Respiratory viruses, including SARS-CoV-2, can trigger chronic lung disease that persists and even progresses after expected clearance of infectious virus. To gain an understanding of this process, we examined a series of consecutive fatal cases of Covid-19 that came to autopsy at 27-51 d after hospital admission. In each patient, we identify a stereotyped bronchiolar-alveolar pattern of lung remodeling with basal epithelial cell hyperplasia and mucinous differentiation. Remodeling regions also feature macrophage infiltration and apoptosis and a marked depletion of alveolar type 1 and 2 epithelial cells. This entire pattern closely resembles findings from an experimental model of post-viral lung disease that requires basal-epithelial stem cell growth, immune activation, and differentiation. The present results thereby provide evidence of possible basal epithelial cell reprogramming in long-term Covid-19 as well and thereby a pathway for explaining and correcting lung dysfunction in this type of disease.
Post-acute sequelae of COVID-19 (PASC) are long-term consequences of SARS-CoV-2 infection that can substantially impair quality of life. Underlying mechanisms ranging from persistent virus to innate and adaptive immune dysregulation have been discussed. Here, we profiled plasma of 181 individuals from the cohort study for digital health research in Germany (DigiHero) including individuals after mild to moderate COVID-19 with or without PASC and uninfected controls. We focused on soluble factors related to monocyte/macrophage biology and on circulating SARS-CoV-2 spike (S1) protein as potential biomarker for persistent viral reservoirs. At a median time of eight months after infection, we found pronounced dysregulation in almost all tested soluble factors including both pro-inflammatory and pro-fibrotic cytokines. These perturbations were remarkably independent of ongoing symptoms, but further correlation and regression analyses suggested PASC specific patterns involving CCL2/MCP-1 and IL-8 as well as long-term persistence of high IL-5 and IL-17F levels. None of the analyzed factors correlated with the detectability or levels of circulating S1 indicating that this represents an independent subset of patients with PASC. This data confirms prior evidence of immune dysregulation and persistence of viral protein in PASC and illustrates its biological heterogeneity that still awaits correlation with clinically defined PASC subtypes.
Background Robust diagnostics, capable of detecting multiple variant of SARS-CoV-2 are necessary to mitigate the COVID-19 pandemic. In this study we directly compare the diagnostic capabilities of an LFI engineered with monoclonal antibodies (mAbs) originating from SARS-CoV-2 NP immunizations to the Abbott BinaxNOW™ COVID-19 Antigen CARD. Methods Here we established a library of 18 mAbs specific to SARS-CoV-2 NP and used two of these mAbs (1CV7 and 1CV14) to generate a prototype antigen-detection lateral flow immunoassay (LFI). Samples consisting of remnant RT-PCR positive patient nasopharyngeal swabs preserved in viral transport media (VTM) were tested on the 1CV7/1CV14 LFI and the commercially available BinaxNOW™ test. Assays were allowed to resolve and results were recorded by two observers. Findings A total of 98 remnant SARS-CoV-2 positive patient specimens were tested on both the 1CV7/1CV14 LFI and the BinaxNOW™ test. The 1CV7/1CV14 LFI detected 71 of the total 98 specimens, while the BinaxNOW™ test detected 52 of the 98 specimens. Additionally, the 1CV7/1CV14 LFI consistently detected samples with higher RT-PCR cycle threshold values than the BinaxNOW™ test. Interpretation The 1CV7/1CV14 LFI outperformed the BinaxNOW™ test in the detection of BA.2, BA.2.12.1, and BA.5 Omicron sub-variants when testing remnant RT-PCR positive patient nasopharyngeal swabs diluted in viral transport media. BA.1 and BA.4 detection was comparable. The data suggest that mAbs derived from SARS-CoV-2 NP can aid in a more sensitive diagnostic immunoassay for COVID-19.
Background The durability and cross-neutralizability of protective antibodies against evolving SARS-CoV-2 variants are primary concerns in mitigating (re-)exposures. The role of antibody maturation, the process whereby selection of higher avidity antibodies augments host immunity, to determine SARS-CoV-2 neutralizability was investigated. Methods Sera collected from SARS-CoV-2 convalescent individuals at 2- or 10-months after recovery, and BNT162b2 vaccine recipients at 3 or 25 weeks post-vaccination, were analyzed. Anti-spike IgG avidity was measured on a urea-treated ELISA platform. Neutralizing ability of antibodies was assessed by surrogate virus neutralization. Fold change between variant and wild-type antigen neutralizability was calculated to infer breadth of neutralizability. Results Compared with early-convalescence, the avidity index of late-convalescent sera was significantly higher (median 37.7 (interquartile range 28.4-45.1) vs. 64.9 (57.5-71.5), p < 0.0001), indicative of progressive antibody maturation extending months beyond acute-phase illness. The urea-resistant, high-avidity fraction of IgG was best predictive of neutralizability (Spearman9s r = 0.49 vs. 0.67 for wild-type; 0.18-0.52 vs. 0.48-0.83 for variants). Higher-avidity convalescent sera showed greater cross-neutralizability against SARS-CoV-2 variants (p < 0.001 for Alpha; p < 0.01 for Delta and Omicron). Vaccinees experienced delayed maturation kinetics, translating to limited breadth of neutralizability at week-25 post-vaccination which was only comparable to that of early-convalescence. Conclusions Avidity maturation grants broader neutralizability that is resilient against emerging SARS-CoV-2 variants. With immunopotentiation through repeat vaccinations becoming a pivotal strategy to accomplish herd immunity, understanding the variable longitudinal evolutions of the two building blocks of hybrid immunity is crucial.
Besides nasopharyngeal swabs, monkeypox virus (MPXV) DNA has been detected in a variety of samples such as saliva, semen, urine and fecal samples. Using the environmental surveillance network previously developed in Spain for the routine wastewater surveillance of SARS-CoV-2 (VATar COVID-19), we have analyzed the presence of MPXV DNA in wastewater from different areas of Spain. Samples (n=312) from 24 different wastewater treatment plants were obtained between May 9 (week 22_19) and August 4 (week 22_31), 2022. Following concentration of viral particles by flocculation, a qPCR procedure allowed us to detect MPXV DNA in 63 wastewater samples collected from May 16 to August 4, 2022, with values ranging between 2.2 per 103 to 8.7 per 104 genome copies (gc)/L. This study shows that MPXV DNA can be reproducibly detected by qPCR in longitudinal samples collected from different Spanish wastewater treatment plants. According to data from the National Epidemiological Surveillance Network (RENAVE) in Spain a total of 6,119 cases have been confirmed as of August 19, 2022. However, and based on the wastewater data, the reported clinical cases seem to be underestimated and asymptomatic infections may be more frequent than expected.
The SEIR model is one of modified models of SIR, specially taken into account of exposed people. SEIR equations can be solved numerically, but it is hard to obtain analytically. Here, we propose some approximate solutions of SEIR equations, one of which is related with the logistic formula in Biology. As the second aim, the SEIR model is applied to the 7-wave of COVID-19 in Japan. The basic reproduction number (α) in the SEIR model is estimated for the Omicron wave. We make use of data of the removed number R(t) rather than that of the infective number, because the latter seems to be ambiguous. This analysis gives α =10 with γ=1 and σ=0.5.
ABSTRACT Background More people with a history of prior infection are receiving SARS-CoV-2 vaccines. Understanding the magnitude of protectivity granted by hybrid immunity, the combined response of infection- and vaccine-induced immunity, may impact vaccination strategies. Methods A total of 36 synchronously infected (prior infection) and, 33 SARS-CoV-2 naive (naive) individuals participated. Participants provided sera six months after completing a round of BNT162b2 vaccination, to be processed for anti-spike antibody measurements and neutralization assays. The relationships between antibody titer, groups and age were explored. Results Anti-spike antibody titers at 6 months post-vaccination were significantly higher, reaching 13- to 17-fold, in the prior infection group. Linear regression models showed that the enhancement in antibody titer attributable to positive infection history increased from 8.9- to 9.4- fold at age 30 to 19- to 32-fold at age 60. Sera from the prior infection group showed higher neutralizing capacity against all six analyzed strains, including the Omicron variant. Conclusions Prior COVID-19 led to establishing enhanced humoral immunity at 6 months after vaccination. Antibody fold-difference attributed to positive COVID-19 history increased with age, possibly because older individuals are prone to symptomatic infection accompanied by potentiated immune responses. Durable protection of hybrid immunity deserves reflection in vaccination campaigns.
Association Between Smell Training and Quality of Life in Patients With Impaired Sense of Smell Following COVID-19 - Condition: COVID-19
Interventions: Other: Olfactory training with essential oils; Other: Olfactory training with fragrance-free oils
Sponsor: Ditte Gertz Mogensen
Recruiting
COVID-19 Fourth Dose Study in Australia - Condition: COVID-19
Interventions: Biological: Tozinameran; Biological: Elasomeran; Biological: Bivalent Pfizer-BioNTech; Biological: Bivalent Moderna
Sponsors: Murdoch Childrens Research Institute; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity
Not yet recruiting
Safety and Effects of an Investigational COVID-19 Vaccine as a Booster in Healthy People - Conditions: SARS-CoV-2 Infection; COVID-19
Interventions: Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg; Biological: BNT162b4 5 µg; Biological: BNT162b4 10 µg; Biological: BNT162b4 15 µg
Sponsors: BioNTech SE; Pfizer
Not yet recruiting
Trial of 2nd Booster Dose of COVID-19 Vaccine - Condition: COVID-19
Intervention: Other: Invitation to get a 2nd booster dose of COVID-19 vaccine
Sponsor: Norwegian Institute of Public Health
Not yet recruiting
SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Text Message Study - Condition: COVID-19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)
Sponsors: University of Utah; Utah Department of Health; Association for Utah Community Health; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)
Not yet recruiting
SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Conversational Agent Study - Condition: COVID-19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Conversational Agent (CA); Behavioral: Patient Navigation (PN)
Sponsors: University of Utah; Utah Department of Health; Association for Utah Community Health; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)
Not yet recruiting
PBI-0451 Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19 - Condition: COVID-19
Interventions: Drug: PBI-0451; Drug: Placebo
Sponsor: Pardes Biosciences, Inc.
Recruiting
Evaluating the Safety and Efficacy of AD17002 Intranasal Spray in Treating Participants With Mild to Moderate COVID-19 - Condition: COVID-19
Interventions: Biological: AD17002 + Formulation buffer; Biological: Placebo
Sponsors: Advagene Biopharma Co. Ltd.; Gadjah Mada University
Not yet recruiting
Community-Based Health Education Programs for the Early Detection of, and Vaccination Against, COVID-19 and the Adoption of Self-Protective Measures of Hong Kong Residents - Condition: COVID-19
Interventions: Behavioral: Community-based Health Education based on core intervention package; Behavioral: Health Information Sharing Group
Sponsors: The Hong Kong Polytechnic University; Food and Health Bureau, Hong Kong
Recruiting
Multidisciplinary Day-hospital Versus Waiting List Management of Post-COVID-19 Persistent Symptoms (ECHAP-COVID) - Condition: Post COVID-19 Condition
Intervention: Behavioral: Personalized multidisciplinary day-hospital intervention
Sponsor: Assistance Publique - Hôpitaux de Paris
Not yet recruiting
Simvastatin Nasal Rinses for the Treatment of COVID-19 Mediated Dysomsia - Conditions: Olfactory Disorder; COVID-19
Intervention: Drug: Simvastatin
Sponsors: Washington University School of Medicine; Duke University
Not yet recruiting
Efficacy and Safety Evaluation of Paxlovid for COVID-19: a Real-world Case-control Study - Condition: COVID-19 Pneumonia
Interventions: Drug: standard-of-care plus Paxlovid; Drug: standard-of-care
Sponsor: Ruijin Hospital
Recruiting
Booster Study of PTX-COVID19-B in Adults Aged 18 Years and Older - Condition: SARS-CoV-2 Infection
Interventions: Biological: PTX-COVID19-B; Biological: Comirnaty®
Sponsor: Everest Medicines (Singapore) Pte. Ltd.
Not yet recruiting
Booster Superiority Study of PTX-COVID19-B Compared to Vaxzevria® in Adults Aged 18 Years and Older - Condition: SARS-CoV-2 Infection
Interventions: Biological: PTX-COVID19-B; Biological: Vaxzevria®
Sponsor: Everest Medicines (Singapore) Pte. Ltd.
Not yet recruiting
Engaging Church Health Ministries to Decrease Coronavirus Disease-19 Vaccine Hesitancy in Underserved Populations - Condition: COVID-19
Intervention: Behavioral: Active Intervention Group
Sponsor: Pennington Biomedical Research Center
Not yet recruiting
Identification and characterization of a novel cell binding and cross-reactive region on spike protein of SARS-CoV-2 - Given that COVID-19 continues to wreak havoc around the world, it is imperative to search for a conserved region involved in viral infection so that effective vaccines can be developed to prevent the virus from rapid mutations. We have established a twelve-fragment library of recombinant proteins covering the entire region of spike protein of both SARS-CoV-2 and SARS-CoV from Escherichia coli. IgGs from murine antisera specifically against 6 spike protein fragments of SARS-CoV-2 were produced,…
Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein - Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available coronavirus disease 2019 vaccines and monoclonal antibody therapies through epitope change on the receptor binding domain of the viral spike glycoprotein. Hence, there is a specific urgent need for alternative antivirals that target processes less likely to be affected by mutation, such as the membrane fusion step of viral entry into the host cell. One such antiviral class includes peptide…
The immunological role of b7-h4 in pregnant women with sars-cov2 infection - CONCLUSIONS: The expression of the immunological marker sB7-H4 correlated with the severity of COVID-19 disease in pregnant women. sB7-H4 and B7-H4 can be used to monitor the progression of COVID-19 infection during pregnancy, and for evaluating of the maternal immune status. This article is protected by copyright. All rights reserved.
Thiopurines inhibit coronavirus Spike protein processing and incorporation into progeny virions - There is an outstanding need for broadly acting antiviral drugs to combat emerging viral diseases. Here, we report that thiopurines inhibit the replication of the betacoronaviruses HCoV-OC43 and SARS-CoV-2. 6-thioguanine (6-TG) disrupted early stages of infection, limiting accumulation of full-length viral genomes, subgenomic RNAs and structural proteins. In ectopic expression models, we observed that 6-TG increased the electrophoretic mobility of Spike from diverse betacoronaviruses, matching…
Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals - SARS-CoV-2 anti-spike antibody concentrations and angiotensin converting enzyme-2 (ACE-2) inhibition have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. We tested the correlation of these measures among vaccinated participants, and examined subgroups based on duration since vaccination and vaccine dosing intervals. We analyzed 120 samples from two-dose mRNA vaccinees without previous COVID-19. We calculated Spearman…
Dietary alpha-ketoglutarate inhibits SARS CoV-2 infection and rescues inflamed lungs to restore O2 saturation by inhibiting pAkt - No abstract
Exploring the mechanism of action of licorice in the treatment of COVID-19 through bioinformatics analysis and molecular dynamics simulation - Purpose: The rapid worldwide spread of Corona Virus Disease 2019 (COVID-19) has become not only a global challenge, but also a lack of effective clinical treatments. Studies have shown that licorice can significantly improve clinical symptoms such as fever, dry cough and shortness of breath in COVID-19 patients with no significant adverse effects. However, there is still a lack of in-depth analysis of the specific active ingredients of licorice in the treatment of COVID-19 and its mechanism of…
Multi-Condition QSAR Model for the Virtual Design of Chemicals with Dual Pan-Antiviral and Anti-Cytokine Storm Profiles - Respiratory viruses are infectious agents, which can cause pandemics. Although nowadays the danger associated with respiratory viruses continues to be evidenced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the virus responsible for the current COVID-19 pandemic, other viruses such as SARS-CoV-1, the influenza A and B viruses (IAV and IBV, respectively), and the respiratory syncytial virus (RSV) can lead to globally spread viral diseases. Also, from a biological point of…
Chestnut inner shell extract inhibits viral entry of porcine epidemic diarrhea virus and other coronaviruses in vitro - Porcine epidemic diarrhea virus (PEDV) is a coronavirus that causes acute diarrhea in suckling piglets. Although vaccines are able to reduce the incidence of PEDV infection, outbreaks of PEDV continue to be reported worldwide and cause serious economic losses in the swine industry. To identify novel antiviral sources, we identified the chestnut (Castanea crenata) inner shell (CIS) as a natural material with activity against PEDV infection in vitro. The ethanol fractions of CIS extracts potently…
Anti-SARS-CoV-2 Activity of Targeted Kinase Inhibitors: Repurposing Clinically Available Drugs for COVID-19 Therapy - CONCLUSIONS: This work supports further evaluation of AXL-targeting kinase inhibitors as potential antiviral agents and treatments for COVID-19. Additional mechanistic studies are needed to determine underlying differences in virus response. This article is protected by copyright. All rights reserved.
Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches - Diminazene aceturate (DIZE), an antiparasitic, is an ACE2 activator, and studies show that activators of this enzyme may be beneficial for COVID-19, disease caused by SARS-CoV-2. Thus, the objective was to evaluate the in silico and in vitro affinity of diminazene aceturate against molecular targets of SARS-CoV-2. 3D structures from DIZE and the proteases from SARS-CoV-2, obtained through the Protein Data Bank and Drug Database (Drubank), and processed in computer programs like AutodockTools,…
More tools for our toolkit: the application of HEL-299 cells and dsRNA-nanoparticles to study human coronaviruses in vitro - Human coronaviruses (HCoVs) are important human pathogens, as exemplified by the current SARS-CoV-2 pandemic. While the ability of type I interferons (IFNs) to limit coronavirus replication has been established, the ability of double-stranded (ds)RNA, a potent IFN inducer, to inhibit coronavirus replication when conjugated to a nanoparticle is largely unexplored. Additionally, the number of IFN competent cell lines that can be used to study coronaviruses in vitro are limited. In the present…
In vitro activity of cysteamine against SARS-CoV-2 variants - Global COVID-19 pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Continuous emergence of new variants and their rapid spread are jeopardizing vaccine countermeasures to a significant extent. While currently available vaccines are effective at preventing illness associated with SARS-CoV-2 infection, these have been shown to be less effective at preventing breakthrough infection and transmission from a vaccinated individual to others. Here we…
Spike mutation resilient scFv76 antibody counteracts SARS-CoV-2 lung damage upon aerosol delivery - Uneven worldwide vaccination coverage against SARS-CoV-2 and emergence of variants escaping immunity call for broadly-effective and easily-deployable therapeutics. We previously described the human single-chain scFv76 antibody, which recognizes SARS-CoV-2 Alfa, Beta, Gamma and Delta variants. We now show that scFv76 also neutralizes infectivity and fusogenic activity of Omicron BA.1 and BA.2 variants. Cryo-EM analysis reveals that scFv76 binds to a well-conserved SARS-CoV-2 spike epitope,…
GSK3326595 is a promising drug to prevent SARS-CoV-2 Omicron and other variants infection by inhibiting ACE2-R671 di-methylation - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 epidemic is worsening. Binding of the Spike1 protein of SARS-CoV-2 with the ACE2 receptor mediates entry of the virus into host cells. Many reports show that protein arginine methylation by PRMTs is important for the functions of these proteins, but it remains unclear whether ACE2 is methylated by PRMTs. Here, we show that PRMT5 catalyses ACE2 symmetric dimethylation at residue R671 (meR671-ACE2). We indicate that…