Background: The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral load and disease severity. Understanding such mechanisms may help to develop treatments and vaccine strategies to reduce transmission. Combining mathematical modelling of URT viral load dynamics with transcriptome analyses we aimed to identify mechanisms controlling URT viral load. Methods: COVID-19 patients were recruited in Spain during the first wave of the pandemic. RNA sequencing of peripheral blood and targeted NanoString nCounter transcriptome analysis of nasal epithelium were performed and gene expression analysed in relation to paired URT viral load samples collected within 15 days of symptom onset. Proportions of major immune cells in blood were estimated from transcriptional data using computational differential estimation. Weighted correlation network analysis (adjusted for cell proportions) and fixed transcriptional repertoire analysis were used to identify associations with URT viral load, quantified as standard deviations (z-scores) from an expected trajectory over time. Results: Eighty-two subjects (50% female, median age 54 years (range 3-73)) with COVID-19 were recruited. Paired URT viral load samples were available for 16 blood transcriptome samples, and 17 respiratory epithelial transcriptome samples. Natural Killer (NK) cells were the only blood cell type significantly correlated with URT viral load z-scores (r = -0.62, P = 0.010). Twenty-four blood gene expression modules were significantly correlated with URT viral load z-score, the most significant being a module of genes connected around IFNA14 (Interferon Alpha-14) expression (r = -0.60, P = 1e-10). In fixed repertoire analysis, prostanoid-related gene expression was significantly associated with higher viral load. In nasal epithelium, only GNLY (granulysin) gene expression showed significant negative correlation with viral load. Conclusions: Correlations between the transcriptional host response and inter-individual variations in SARS-CoV-2 URT viral load, revealed many molecular mechanisms plausibly favouring or constraining viral load. Existing evidence corroborates many of these mechanisms, including likely roles for NK cells, granulysin, prostanoids and interferon alpha-14. Inhibition of prostanoid production, and administration of interferon alpha-14 may be attractive transmission-blocking interventions.
The COVID-19 pandemy has created a radically new situation where most countries provide raw measurements of their daily incidence and disclose them in real time. This enables new machine learning forecast strategies where the prediction might no longer be based just on the past values of the current incidence curve, but could take advantage of observations in many countries. We present such a simple global machine learning procedure using all past daily incidence trend curves. Each of the 27,418 COVID-19 incidence trend curves in our database contains the values of 56 consecutive days extracted from observed incidence curves across 61 world regions and countries. Given a current incidence trend curve observed over the past four weeks, its forecast in the next four weeks is computed by matching it with the first four weeks of all samples, and ranking them by their similarity to the query curve. Then the 28 days forecast is obtained by a statistical estimation combining the values of the 28 last observed days in those similar samples. Using comparison performed by the European Covid-19 Forecast Hub with the current state of the art forecast methods, we verify that the proposed global learning method, EpiLearn, compares favorably to methods forecasting from a single past curve.
Background: Medical oxygen is an essential component of modern healthcare, with a wide variety of applications ranging from supplemental use in surgery and trauma patients to the primary medication in oxygen therapy. This is the most effective treatment for any respiratory illness. Despite the importance of oxygen for public health and its demand as a life-saving drug, research on the subject is limited, with the majority of studies conducted following the outbreak of the COVID-19 pandemic. Due to the lack of empirical studies, we aimed to compile the recent research efforts with the current state of the field through a systematic review. Methods: We have performed a systematic review targeting the medical oxygen ecosystem, following the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P). For the study, we have limited our scope to healthcare facilities and domiciliary applications of medical oxygen. We considered the articles published in the last twenty years, starting from the SARS outbreak in November 2002 to 15th May 2022. Results: Our systematic search resulted in forty-one preliminary articles, with three more articles appended for a complete outlook on the topic. Based on the selected articles, the current state of the topic was presented through detailed discussion and analysis. Conclusion: We have presented an in-depth discussion of the research works found through the systematic search while extrapolating to provide insights on the current subject scenario. We have highlighted the areas with inadequate contemporary studies and presented some research gaps in the field.
Aims and objectives: This study demonstrates the impact of the full liberalization of COVID-19 on the psychological issues and the prevalence rate and associated factors of depressive symptoms, anxiety, and insomnia among frontline nurses. Background: It has been demonstrated that frontline nurses fighting against the epidemic were under great psychological stress. However, there is a lack of studies assessing the prevalence rates of anxiety, depression, and insomnia among frontline nurses after the full liberalization of COVID-19 in China. Design: Cross-sectional study. Methods: Of 1766 frontline nurses were invited to complete a self-reported online questionnaire by convenience sampling. The survey included six main sections: the Patient Health Questionnaire, the Generalized Anxiety Disorder Scale, the Insomnia Severity Index, the Perceived Stress Scale, sociodemographic information, and work information. Multiple logistic regression analyses were applied to identify the potential risk factors for psychological issues. Reporting of this research according to the STROBE checklist. Results: 90.83% of frontline nurses were infected with COVID-19, and 33.64% had to work while infected COVID-19. The overall prevalence of depressive symptoms, anxiety and insomnia among frontline nurses was 69.20%, 62.51%, and 76.78%, respectively. Multiple logistic analyses revealed that job satisfaction, attitude toward the current pandemic management, and perceived stress were associated with depressive symptoms, anxiety, and insomnia. Conclusions: This study demonstrated that the full liberalization of COVID-19 had a significant psychological impact on frontline nurses. Early detection of mental health issues and preventive and promotive interventions should be implemented according to the associated factors to improve mental health of nurses. Relevance to clinical practice: This study highlighted that nurses were suffering from varying degrees of depressive symptoms, anxiety, and insomnia, which needed early screening and preventive and promotive interventions for preventing a more serious psychological impact on frontline nurses.
Phase I Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102) - Condition: COVID-19
Intervention: Biological: Recombinant variant COVID-19 vaccine(Sf9 cell)
Sponsor: WestVac Biopharma Co., Ltd.
Not yet recruiting
A Study to Compare QLS1128 With Placebo in Symptomatic Participants With Mild to Moderate COVID-19 - Condition: COVID-19
Interventions: Drug: QLS1128; Drug: Placebo
Sponsor: Qilu Pharmaceutical Co., Ltd.
Not yet recruiting
Effect of Selected Types of Breathing Exercises on Different Outcome Measures in Covid-19 Patients - Condition: COVID-19
Intervention: Other: breathing exercise
Sponsor: Basma Mosaad Abd-elrahman Abushady
Completed
Effect Of Calcitriol On Neutrophil To Lymphocytes Ratio And High Sensitivity C-Reactive Protein Covid-19 Patients - Condition: COVID-19
Interventions: Drug: Calcitriol; Other: Placebo
Sponsor: Universitas Sebelas Maret
Completed
Immunogenicity and Reactogenicity of the 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 - Conditions: Vaccine Reaction; COVID-19
Interventions: Biological: Comirnaty® BNT162b2 /Omicron BA.4-5 vaccine (Pfizer-BioNTech); Biological: VidPrevtyn® Beta vaccine (Sanofi/GSK)
Sponsors: Assistance Publique - Hôpitaux de Paris; IREIVAC/COVIREIVAC Network
Not yet recruiting
Study of WPV01 Compared With Placebo in Patients With Mild/Moderate COVID-19 Infection - Condition: COVID-19 Infection
Interventions: Drug: WPV01; Drug: Placebo
Sponsor: Westlake Pharmaceuticals (Hangzhou) Co., Ltd.
Not yet recruiting
ARVAC-A New Recombinant Coronavirus Disease 2019 (COVID-19) - Condition: COVID-19 Vaccine
Interventions: Biological: Gamma Variant RBD-based ARVAC-CG vaccine; Biological: Omicron Variant RBD-based ARVAC-CG vaccine; Biological: Bivalent RBD-based ARVAC-CG vaccine; Other: Placebo
Sponsors: Mónica Edith Lombardo; Universidad Nacional de San Martín (UNSAM); National Council of Scientific and Technical Research, Argentina; Laboratorio Pablo Cassará S.R.L.
Recruiting
A Study of HH-120 Nasal Spray in Close Contacts of Those Diagnosed With COVID-19 - Conditions: COVID-19; SARS-CoV-2 Infection
Intervention: Drug: HH-120 Nasal Spray
Sponsor: Beijing Ditan Hospital
Completed
Oxygen Atomizing Inhalation of EGCG in the Treatment COVID-19 Pneumonia in Cancer Patients - Conditions: COVID-19 Pneumonia; Neoplasms Malignant
Interventions: Drug: EGCG; Drug: Placebo
Sponsor: Shandong Cancer Hospital and Institute
Recruiting
The Use of Photobiomodulation in the Treatment of Oral Complaints of Long COVID-19.A Randomized Controlled Trial. - Conditions: Xerostomia; COVID-19; Long COVID; Persistent COVID-19
Interventions: Combination Product: Institutional standard treatment for xerostomia and Long Covid; Radiation: Photobiomodulation Therapy; Radiation: Placebo Photobiomodulation Therapy
Sponsor: University of Nove de Julho
Recruiting
Acupuncture for Post COVID-19 Fatigue - Conditions: Acupuncture; Post COVID-19 Condition; Fatigue
Interventions: Device: Acupuncture; Device: Sham Acupuncture
Sponsor: Guang’anmen Hospital of China Academy of Chinese Medical Sciences
Not yet recruiting
Balneotherapy for Patients With Post-acute Coronavirus Disease (COVID) Syndrome - Condition: Post-COVID-19 Syndrome
Intervention: Other: Balneotherapy and aquatic exercises
Sponsors: Parc de Salut Mar; Caldes de Montbui’s City Council; Consorcio Centro de Investigación Biomédica en Red (CIBER); European Regional Development Fund
Completed
A Study to Assess the Efficacy of HH-120 Nasal Spray for Prevention of SARS-CoV-2 Infection in Adult Close Contacts of Individuals Infected With SARS-CoV-2 - Condition: SARS-CoV-2 Infection
Interventions: Drug: HH-120 nasal spray 1; Drug: HH-120 nasal spray 2; Drug: Placebo Comparator 1; Drug: Placebo Comparator 2
Sponsor: Beijing Ditan Hospital
Completed
Lactoferrin for COVID-19-Induced Taste or Smell Abnormality - Conditions: Covid19; Taste Disorder, Secondary; Taste Disorders; Dysgeusia; Smell Disorder; Ageusia; Anosmia
Intervention: Dietary Supplement: Lactoferrin
Sponsor: Wake Forest University Health Sciences
Withdrawn
tDCS in Post-COVID Syndrome: Comparison of Two Targets - Conditions: COVID-19; Post-COVID-19 Syndrome; Post COVID-19 Condition
Intervention: Device: transcranial current direct stimulation
Sponsor: Hospital San Carlos, Madrid
Recruiting
Paving New Roads Using Allium sativum as a Repurposed Drug and Analyzing its Antiviral Action Using Artificial Intelligence Technology - CONCLUSIONS: The COVID-19 pandemic has triggered interest among researchers to conduct future research on molecular docking with clinical trials before releasing salutary remedies against the deadly malady.
Brevicillin, a novel lanthipeptide from the genus Brevibacillus with antimicrobial, antifungal and antiviral activity - CONCLUSION: This study provides detailed description of a novel lanthipeptide and demonstrates its effective antibacterial, antifungal and anti-SARS-CoV-2 activity.
Evaluation of residual humoral immune response against SARS-CoV-2 by a surrogate virus neutralization test (sVNT) 9 months after BNT162b2 primary vaccination - The humoral response to SARS-CoV-2 vaccination has shown to be temporary, although may be more prolonged in vaccinated individuals with a history of natural infection. We aimed to study the residual humoral response and the correlation between anti-Receptor Binding Domain (RBD) IgG levels and antibody neutralizing capacity in a population of health care workers (HCWs) after 9 months from COVID-19 vaccination. In this cross-sectional study, plasma samples were screened for anti-RBD IgG using a…
Evaluation of Antiviral Activity of Gemcitabine Derivatives against Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus 2 - Gemcitabine is a nucleoside analogue of deoxycytidine and has been reported to be a broad-spectrum antiviral agent against both DNA and RNA viruses. Screening of a nucleos(t)ide analogue-focused library identified gemcitabine and its derivatives (compounds 1, 2a, and 3a) blocking influenza virus infection. To improve their antiviral selectivity by reducing cytotoxicity, 14 additional derivatives were synthesized in which the pyridine rings of 2a and 3a were chemically modified….
A novel mAb broadly neutralizes SARS-CoV-2 VOCs in vitro and in vivo, including the Omicron variants - Novel immune escape variants have emerged as SARS-CoV-2 continues to spread worldwide. Many of the variants cause breakthrough infections in vaccinated populations, posing great challenges to current antiviral strategies targeting the immunodominance of the receptor-binding domain within the spike protein. Here, we found that a novel broadly neutralizing monoclonal antibody (mAb), G5, provided efficient protection against SARS-CoV-2 variants of concern (VOCs) in vitro and in vivo. A single dose…
Mucosal immunization with Ad5-based vaccines protects Syrian hamsters from challenge with omicron and delta variants of SARS-CoV-2 - SARS-CoV-2 variant clades continue to circumvent antibody responses elicited by vaccination or infection. Current parenteral vaccination strategies reduce illness and hospitalization, yet do not significantly protect against infection by the more recent variants. It is thought that mucosal vaccination strategies may better protect against infection by inducing immunity at the sites of infection, blocking viral transmission more effectively, and significantly inhibiting the evolution of new…
2-Deoxy-D-Glucose: A Novel Pharmacological Agent for Killing Hypoxic Tumor Cells, Oxygen Dependence-Lowering in Covid-19, and Other Pharmacological Activities - The nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DG) has shown promising pharmacological activities, including inhibition of cancerous cell growth and N-glycosylation. It has been used as a glycolysis inhibitor and as a potential energy restriction mimetic agent, inhibiting pathogen-associated molecular patterns. Radioisotope derivatives of 2-DG have applications as tracers. Recently, 2-DG has been used as an anti-COVID-19 drug to lower the need for supplemental oxygen. In the present…
Potential Regulation of NF-κB by Curcumin in Coronavirus-Induced Cytokine Storm and Lung Injury - The current pandemic coronavirus disease-19 (COVID-19) is still a global medical and economic emergency with over 244 million confirmed infections and over 4.95 million deaths by October 2021, in less than 2 years. Severe acute respiratory syndrome (SARS), the Middle East respiratory syndrome coronavirus (MERS), and COVID-19 are three recent coronavirus pandemics with major medical and economic implications. Currently, there is no effective treatment for these infections. One major pathological…
Type I interferon signaling induces a delayed antiproliferative response in Calu-3 cells during SARS-CoV-2 infection - Disease progression during SARS-CoV-2 infection is tightly linked to the fate of lung epithelial cells, with severe cases of COVID-19 characterized by direct injury of the alveolar epithelium and an impairment in its regeneration from progenitor cells. The molecular pathways that govern respiratory epithelial cell death and proliferation during SARS-CoV-2 infection, however, remain poorly understood. We now report a high-throughput CRISPR screen for host genetic modifiers of the survival and…
Induction of systemic, mucosal, and cellular immunity against SARS-CoV-2 in mice vaccinated by trans-airway with a S1 protein combined with a pulmonary surfactant-derived adjuvant SF-10 - CONCLUSIONS: Based on the need for effective systemic, respiratory, and cellular immunity, the S1-SF-10-TA vaccine seems promising mucosal vaccine against respiratory infection of SARS-CoV-2.
SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in individuals with multiple sclerosis receiving different disease-modifying treatments - INTRODUCTION: The study aims to evaluate the concentration of IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike1 protein (S1RBD) in BNT162b2- vaccinated relapsing-remitting multiple sclerosis (RRMS) individuals receiving disease-modifying treatments (DMTs).
miRNAs derived from milk small extracellular vesicles inhibit porcine epidemic diarrhea virus infection - Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus in the family Coronaviridae, causes acute diarrhea and/or vomiting, dehydration, and high mortality in neonatal piglets. It has caused huge economic losses to animal husbandry worldwide. Current commercial PEDV vaccines do not provide enough protection against variant and evolved virus strains. No specific drugs are available to treat PEDV infection. The development of more effective therapeutic anti-PEDV agents is…
Ovatodiolide inhibits SARS-CoV-2 replication and ameliorates pulmonary fibrosis through suppression of the TGF-β/TβRs signaling pathway - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to pose threats to public health. The clinical manifestations of lung pathology in COVID-19 patients include sustained inflammation and pulmonary fibrosis. The macrocyclic diterpenoid ovatodiolide (OVA) has been reported to have anti-inflammatory, anti-cancer, anti-allergic, and analgesic activities. Here, we investigated the pharmacological mechanism of OVA in suppressing SARS-CoV-2 infection and pulmonary fibrosis…
Neutralizing activity and 3-month durability of tixagevimab and cilgavimab prophylaxis against Omicron sublineages in transplant recipients - Neutralizing antibody (nAb) responses are attenuated in solid organ transplant recipients (SOTRs) despite severe acute respiratory syndrome-coronavirus-2 vaccination. Preexposure prophylaxis (PrEP) with the antibody combination tixagevimab and cilgavimab (T+C) might augment immunoprotection, yet in vitro activity and durability against Omicron sublineages BA.4/5 in fully vaccinated SOTRs have not been delineated. Vaccinated SOTRs, who received 300 + 300 mg T+C (ie, full dose), within a…
Therapeutic potential of salicylamide derivatives for combating viral infections - Since time immemorial human beings have constantly been fighting against viral infections. The ongoing and devastating coronavirus disease 2019 pandemic represents one of the most severe and most significant public health emergencies in human history, highlighting an urgent need to develop broad-spectrum antiviral agents. Salicylamide (2-hydroxybenzamide) derivatives, represented by niclosamide and nitazoxanide, inhibit the replication of a broad range of RNA and DNA viruses such as flavivirus,…