Background: Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. Methods and Findings: In this study, we compared COVID-19 ARDS (n=43) and bacterial sepsis-induced (non-COVID-19) ARDS (n=24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. Conclusion: We present a first comprehensive molecular characterization of differences between two ARDS etiologies: COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions.
Building realistically complex models of infectious disease transmission that are relevant for informing public health is conceptually challenging and requires knowledge of coding architecture that can implement key modeling conventions. For example, many of the models built to understand COVID-19 dynamics have included stochasticity, transmission dynamics that change throughout the epidemic due to changes in host behavior or public health interventions, and spatial structures that account for important spatio-temporal heterogeneities. Here we introduce an R package, SPARSEMODr, that allows users to simulate disease models that are stochastic and spatially explicit, including a model for COVID-19 that was useful in the early phases of the epidemic. SPARSEMOD stands for SPAtial Resolution-SEnsitive Models of Outbreak Dynamics, and our goal is to demonstrate particular conventions for rapidly simulating the dynamics of more complex, spatial models of infectious disease. In this report, we outline the features and workflows of our software package that allow for user-customized simulations. We believe the example models provided in our package will be useful in educational settings, as the coding conventions are adaptable, and will help new modelers to better understand important assumptions that were built into sophisticated COVID-19 models.
There is limited understanding of antibody responses in children across different SARS-CoV-2 variants. As part of an ongoing household cohort study, we assessed the antibody response among unvaccinated children infected with Wuhan, Delta or Omicron variants, as well as vaccinated children with breakthrough Omicron infection, using a SARS-CoV-2 S1-specific IgG assay and surrogate virus neutralisation test (sVNT). Most children infected with Delta (100%, 35/35) or Omicron (81.3%, 13/16) variants seroconverted by one month following infection. In contrast, 37.5% (21/56) children infected with Wuhan seroconverted, as previously reported. However, Omicron-infected children (GMC 46.4 BAU/ml; sVNT % inhibition: 16.3%) mounted a significantly lower antibody response than Delta (435.5 BAU/mL, sVNT=76.9%) or Wuhan (359.0 BAU/mL, sVNT=74.0%). Vaccinated children with breakthrough Omicron infection mounted the highest antibody response (2856 BAU/mL, sVNT=96.5%). Our findings suggest that despite a high seroconversion rate, Omicron infection in children results in lower antibody levels and function compared with Wuhan or Delta infection or with vaccinated children with breakthrough Omicron infection. Our data have important implications for public health measures and vaccination strategies to protect children.
The emergence of novel Omicron lineages, such as BA.5, may impact the therapeutic efficacy of anti-SARS-CoV-2 neutralizing monoclonal antibodies (mAbs). Here, we evaluated the neutralization and ADCC activity of 6 therapeutic mAbs against Delta, BA.2, BA.4 and BA.5 isolates. The Omicron sub-variants escaped most of the antibodies but remained sensitive to Bebtelovimab and Cilgavimab. Consistent with their shared spike sequence, BA.4 and BA.5 displayed identical neutralization profiles. Sotrovimab was the most efficient at eliciting ADCC. We also analyzed 121 sera from 40 immunocompromised individuals up to 6 months after infusion of 1200 mg of Ronapreve (Imdevimab + Casirivimab), and 300 or 600 mg of Evusheld (Cilgavimab + Tixagevimab). Sera from Ronapreve-treated individuals did not neutralize Omicron subvariants. Evusheld-treated individuals neutralized BA.2 and BA.5, but titers were reduced by 41- and 130-fold, respectively, compared to Delta. A longitudinal evaluation of sera from Evusheld-treated patients revealed a slow decay of mAb levels and neutralization. The decline was more rapid against BA.5. Our data shed light on the antiviral activities of therapeutic mAbs and the duration of effectiveness of Evusheld pre-exposure prophylaxis.
Immunosuppressed patients have increased risk for morbidity and mortality from COVID-19 because they less frequently mount antibody responses to vaccines and often cannot tolerate small-molecule antivirals. The Omicron variant of concern of SARS-CoV-2 has progressively defeated anti-Spike mAbs authorized so far, paving the way to a return to COVID-19 convalescent plasma (CCP) therapy. In this systematic review we performed a metanalysis of 8 controlled studies (totaling 469 treated patients and 1305 controls and including 3 randomized controlled trials), an individual patient data analysis of 125 case reports/series (totaling 265 patients), and a descriptive analysis of 13 uncontrolled large case series without individual patient data available (totaling 358 patients). The metanalysis of controlled studies showed a risk ratio for mortality of 0.63 (0.58 in randomized controlled trials) in treatment with CCP versus standard of care for immunosuppressed COVID-19 patients. On the basis of this evidence, we encourage initiation of high-titer CCP from vaccinees (hybrid plasma) in immunocompromised patients.
In mid-2021, the SARS-CoV-2 Delta variant caused the third wave of the COVID-19 pandemic in several countries worldwide. The pivotal studies were aimed at studying changes in the efficiency of neutralizing antibodies to the spike protein. However, much less attention was paid to the T-cell response and the presentation of virus peptides by MHC-I molecules. In this study, we compared the features of the HLA-I genotype in symptomatic patients with COVID-19 in the first and third waves of the pandemic. As a result, we could identify the vanishing of carriers of the HLA-A01:01 allele in the third wave and demonstrate the unique properties of this allele. Thus, HLA-A01:01-binding immunodominant epitopes are mostly derived from ORF1ab. A set of epitopes from ORF1ab was tested, and their high immunogenicity was confirmed. Moreover, analysis of the results of single-cell phenotyping of T-cells in recovered patients showed that the predominant phenotype in HLA-A*01:01 carriers is central memory T-cells. The predominance of T-lymphocytes of this phenotype may contribute to forming long-term T-cell immunity in carriers of this allele. Our results can be the basis for highly effective vaccines based on ORF1ab peptides.
Mobility data have demonstrated major changes in human movement patterns in response to COVID-19 and associated interventions in many countries. This can involve sub-national redistribution, short-term relocations as well as international migration. In this paper, we combine detailed location data from Facebook measuring the location of approximately 6 million daily active Facebook users in 5km2 tiles in the UK with census-derived population estimates to measure population mobility and redistribution. We provide time-varying population estimates and assess spatial population changes with respect to population density and four key reference dates in 2020 (First lockdown, End of term, Beginning of term, Christmas). We also show how population estimates derived from the distribution of Facebook users vary compared to mid-2020 small area population estimates by the UK national statistics agencies. We estimate that between March 2020 and March 2021, the total population of the UK declined and we identify important spatial variations in this population change, showing that low-density areas have experienced lower population decreases than urban areas. We estimate that, for the top 10% highest population tiles, the population has decreased by 6.6%. Further, we provide evidence that geographic redistributions of population within the UK coincide with dates of non-pharmaceutical interventions including lockdowns and movement restrictions, as well as seasonal patterns of migration around holiday dates. The methods used in this study reveal significant changes in population distribution at high spatial and temporal resolutions that have not previously been quantified by available demographic surveys in the UK. We found early indicators of potential longer-term changes in the population distribution of the UK although it is not clear if these changes may persist after the COVID-19 pandemic.
A Study to Measure the Amount of Study Medicine in Blood in Adult Participants With COVID-19 and Severe Kidney Disease - Condition: COVID-19
Intervention: Drug: PF-07321332 (nirmatrelvir)/ritonavir
Sponsor: Pfizer
Not yet recruiting
Cognitive Rehabilitation in Post-COVID-19 Condition - Condition: COVID-19
Intervention: Behavioral: Goal Management Training (GMT)
Sponsors: Lovisenberg Diakonale Hospital; University of Oslo; Icahn School of Medicine at Mount Sinai; University of Toronto; UiT The Arctic University of Norway; Oslo University Hospital
Not yet recruiting
A Study of Booster Immunization With COVID-19 Vaccine,Inactivated Co -Administration With Influenza Vaccine and Pneumococcal Polysaccharide Vaccine - Condition: COVID-19
Interventions: Biological: Adult group in immunogenicity and safety study of combined immunization; Biological: Elderly group in immunogenicity and safety study of combined immunization; Biological: Adult group in safety observation study of combined immunization; Biological: Elderly group in safety observation study of combined immunization
Sponsor: Sinovac Biotech Co., Ltd
Completed
EFFECTS OF INSPIRATORY MUSCLE TRAINING IN POST-COVID-19 PATIENTS - Condition: Covid19
Interventions: Other: TREATMENT GROUP (TG); Other: CONTROL GROUP (CG)
Sponsor: University Vila Velha
Completed
Long-term Effects of SARS-CoV-2 on the Central Nervous System and One-year Follow-up of “Long COVID-19” Patients - Condition: Long Covid19
Intervention: Diagnostic Test: Perfusion brain scintigraphy imaging
Sponsor: Brugmann University Hospital
Recruiting
Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome - Condition: Post-COVID-19 Syndrome
Interventions: Drug: Temelimab 54mg/kg; Drug: Placebo
Sponsor: GeNeuro SA
Not yet recruiting
Active Cycle Of Breathing Technique Verses Breathing Exercises In Post ICU COVID-19 Patients - Condition: Post Covid-19 Patients
Interventions: Other: Chest physiotherapy with breathing exercises and ACBT; Other: Chest physiotherapy with breathing exercises
Sponsor: Riphah International University
Recruiting
Addressing Vaccine Hesitancy and Increasing COVID-19 Vaccine Uptake Among African American Young Adults in the South - Conditions: COVID-19; Vaccine Uptake
Intervention: Behavioral: Tough Talks COVID
Sponsors: University of North Carolina, Chapel Hill; University of Alabama at Birmingham; National Institute on Minority Health and Health Disparities (NIMHD)
Not yet recruiting
rSIFN-co Among Healthy Subjects and Subjects With Mild or Asymptomatic COVID-19 - Conditions: COVID-19; SARS-CoV-2
Interventions: Drug: rSIFN-co Nasal Spray; Drug: Placebo Nasal Spray
Sponsor: Sichuan Huiyang Life Science and Technology Corporation
Recruiting
Evaluation of Safety and Immunogenicity of the Recombinant ZR202-CoV and ZR202a-CoV Vaccines in Adults. - Conditions: SARS-CoV-2 Infection; COVID-19
Interventions: Biological: ZR202-CoV; Biological: ZR202a-CoV; Biological: Comirnaty®
Sponsor: Shanghai Zerun Biotechnology Co.,Ltd
Recruiting
The Effect of Pilates on Biopsychosocial Characteristics in the Covid-19 Pandemic - Conditions: COVID-19; Healthy; Sedentary; Exercise; Pilates
Interventions: Behavioral: Sedantary; Behavioral: Exercise therapy
Sponsor: Medipol University
Recruiting
This Trial is a Clinical Performance Validation Study That Will Evaluate the Clinical Agreement of the Sky Medical™ Rapid Antigen Test Comparing the Antigen Rapid Test to RT-PCR - Conditions: COVID-19; Sars-CoV-2 Infection
Intervention: Diagnostic Test: Sky Medical™ Rapid Antigen Test
Sponsor: Sky Medical Supplies & Equipments, LLC
Recruiting
The Effect Of Distraction Methods On Fear And Anxiety In Children Before The Covid 19 Test - Conditions: Anxiety; Fear
Interventions: Behavioral: The Kaleidescope; Behavioral: The visual illusion cards
Sponsor: Ondokuz Mayıs University
Completed
Cardiovascular Function and Physical Activity in COVID-19 - Condition: Coronavirus 2019
Intervention: Behavioral: Active-at-home-HF
Sponsor: Coventry University
Recruiting
The Effect Of Tele-Exercise Program Applied To Children With Cystic Fibrosis on Quality of Life in Covid 19 Pandemic - Conditions: Cystic Fibrosis; Exercise Addiction; Nursing Caries; Quality of Life; Exercise Adherence
Interventions: Behavioral: Tele-Exercise Program; Behavioral: Just observation
Sponsor: Ondokuz Mayıs University
Completed
Proteomic analysis and identification reveal the anti-inflammatory mechanism of clofazimine on lipopolysaccharide-induced acute lung injury in mice - CONCLUSION: This study can provide significant insight into the proteomics-guided pharmacological mechanism study of CFZ and suggest potential therapeutic strategies for infectious disease.
Modeling SARS-CoV-2 and influenza infections and antiviral treatments in human lung epithelial tissue equivalents - There is a critical need for physiologically relevant, robust, and ready-to-use in vitro cellular assay platforms to rapidly model the infectivity of emerging viruses and develop new antiviral treatments. Here we describe the cellular complexity of human alveolar and tracheobronchial air liquid interface (ALI) tissue models during SARS-CoV-2 and influenza A virus (IAV) infections. Our results showed that both SARS-CoV-2 and IAV effectively infect these ALI tissues, with SARS-CoV-2 exhibiting a…
Structure-Based Identification of Naphthoquinones and Derivatives as Novel Inhibitors of Main Protease Mpro and Papain-like Protease PLpro of SARS-CoV-2 - The worldwide COVID-19 pandemic caused by the coronavirus SARS-CoV-2 urgently demands novel direct antiviral treatments. The main protease (M^(pro)) and papain-like protease (PL^(pro)) are attractive drug targets among coronaviruses due to their essential role in processing the polyproteins translated from the viral RNA. In this study, we virtually screened 688 naphthoquinoidal compounds and derivatives against M^(pro) of SARS-CoV-2. Twenty-four derivatives were selected and evaluated in…
SARS-CoV-2 infection and C1-esterase inhibitor: Camouflage pattern and new perspective - In Covid-19, the pathological effect of SARS-CoV-2 infection is arbitrated through direct viral toxicity, unusual immune response, endothelial dysfunction, deregulated renin-angiotensin system [RAS], and thrombo-inflammation leading to acute lung injury [ALI], with a succession of acute respiratory distress syndrome [ARDS] in critical conditions. C1 esterase inhibitor [C1INH] is a protease inhibitor that inhibits the spontaneous activation of complement and contact systems and kinin pathway,…
The effect of reparixin on survival in patients at high risk for in-hospital mortality: a meta-analysis of randomized trials - CONCLUSION: Our meta-analysis of randomized trials suggests that short-term inhibition of CXCL8 activity improved survival in patients at high risk for in-hospital mortality without increasing the risk of infection.
Phytochemical Discrimination, Biological Activity and Molecular Docking of Water-Soluble Inhibitors from Saussurea costus Herb against Main Protease of SARS-CoV-2 - Siddha medicine is one of the oldest medical systems in the world and is believed to have originated more than 10,000 years ago and is prevalent across ancient Tamil land. It is undeniable that inhibitor preferences rise with increasing solubility in water due to the considerations pertaining to the bioavailability and the ease of which unabsorbed residues can be disposed of. In this study, we showed the phytochemical discrimination of Saussurea costus extracted with water at room temperature as…
Antiviral and Antibacterial Effect of Honey Enriched with Rubus spp. as a Functional Food with Enhanced Antioxidant Properties - The aim of this study was to investigate the effect of blackberry and raspberry fruits (1 and 4%) and leaves (0.5 and 1%) on the biological activities of rape honey. Honey and plant material extracts were analyzed regarding total phenolic, flavonoid, anthocyanin contents, HPTLC and HPLC polyphenol profiles, as well as antioxidant activity. The antiviral potential was analyzed against bacteriophage phi 6-a coronavirus surrogate-whereas antimicrobial was tested against S. aureus and E. coli….
Actions of Novel Angiotensin Receptor Blocking Drugs, Bisartans, Relevant for COVID-19 Therapy: Biased Agonism at Angiotensin Receptors and the Beneficial Effects of Neprilysin in the Renin Angiotensin System - Angiotensin receptor blockers (ARBs) used in the treatment of hypertension and potentially in SARS-CoV-2 infection exhibit inverse agonist effects at angiotensin AR1 receptors, suggesting the receptor may have evolved to accommodate naturally occurring angiotensin ‘antipeptides’. Screening of the human genome has identified a peptide (EGVYVHPV) encoded by mRNA, complementary to that encoding ANG II itself, which is an inverse agonist. Thus, opposite strands of DNA encode peptides with opposite…
Textiles Functionalized with Copper Oxides: A Sustainable Option for Prevention of COVID-19 - COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and healthcare-associated infections (HAIs) represent severe problems in health centers and public areas. Polyester/cotton (PES/CO) blend fabrics have been functionalized with copper oxides on an industrial scale. For functionalization, the impregnation dyeing technique was applied. The functionalized samples were tested virologically against SARS-CoV-2 and human coronavirus (229E) according to ISO 18184-2019 and…
Isolation and In Silico Inhibitory Potential against SARS-CoV-2 RNA Polymerase of the Rare Kaempferol 3-O-(6″-O-acetyl)-Glucoside from Calligonum tetrapterum - The phytochemical constituents of Calligonum tetrapterum Jaub. & Spach (Family Polygonaceae) were studied for the first time. The study resulted in the isolation of the rare flavonol glycoside, kaempferol 3-O-(6″-O-acetyl)-glucoside,(K3G-A). The potential inhibitive activity of K3G-A toward SARS-CoV-2 was investigated utilizing several in silico approaches. First, molecular fingerprints and structural similarity experiments were carried out for K3G-A against nine co-crystallized ligands of nine…
A Systematic Study on the Optimal Nucleotide Analogue Concentration and Rate Limiting Nucleotide of the SARS-CoV-2 RNA-Dependent RNA Polymerase - The current COVID-19 pandemic has highlighted the necessity of more efficient antiviral compounds. The antiviral efficacy of adenosine-based analogs, the main repurposed drugs for SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibition, is mainly assessed through in vitro or cell-free polymerization assays, under arbitrary conditions that do not reflect the physiological environment. We show that SARS-CoV-2 RdRp inhibition efficiency of remdesivir and cordycepin, two common adenosine analogs,…
Serum of Post-COVID-19 Syndrome Patients with or without ME/CFS Differentially Affects Endothelial Cell Function In Vitro - A proportion of COVID-19 reconvalescent patients develop post-COVID-19 syndrome (PCS) including a subgroup fulfilling diagnostic criteria of Myalgic encephalomyelitis/Chronic Fatigue Syndrome (PCS/CFS). Recently, endothelial dysfunction (ED) has been demonstrated in these patients, but the mechanisms remain elusive. Therefore, we investigated the effects of patients’ sera on endothelia cells (ECs) in vitro. PCS (n = 17), PCS/CFS (n = 13), and healthy controls (HC, n = 14) were screened for serum…
Innate Immune Response and Inflammasome Activation During SARS-CoV-2 Infection - The novel coronavirus SARS-CoV-2, responsible for the COVID-19 outbreak, has become a pandemic threatening millions of lives worldwide. Recently, several vaccine candidates and drugs have shown promising effects in preventing or treating COVID-19, but due to the development of mutant strains through rapid viral evolution, urgent investigations are warranted in order to develop preventive measures and further improve current vaccine candidates. Positive-sense-single-stranded RNA viruses comprise…
Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease - SARS-CoV-2 papain-like protease (PLpro) covers multiple functions. Beside the cysteine-protease activity, facilitating cleavage of the viral polypeptide chain, PLpro has the additional and vital function of removing ubiquitin and ISG15 (Interferon-stimulated gene 15) from host-cell proteins to support coronaviruses in evading the host’s innate immune responses. We identified three phenolic compounds bound to PLpro, preventing essential molecular interactions to ISG15 by screening a natural…
Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update - CONCLUSIONS: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers.