Background: Measurement of SARS-CoV-2 antibody seropositivity is important to accurately understand exposure to infection and/or vaccination in specific populations. Methods: Children with or without prior SARS-CoV-2 infections, was enrolled in Calgary, Canada in 2020. Venous blood was sampled 4 times from July 2020 to April 2022 for SARS-CoV-2 nucleocapsid and spike antibodies. Demographic and clinical information was obtained including SARS-CoV-2 testing results and vaccination records. Results: 1035 children were enrolled and 88.9% completed all 4 visits; median age 9 years (IQR: 5,13); 519 (50.1%) female; and 815 (78.7%) Caucasian. Before enrollment, 118 (11.4%) had confirmed or probable SARS-CoV-2. By April 2022, 39.5% of previously uninfected participants had a SARS-CoV-2 infection. Nucleocapsid antibody seropositivity declined to 16.4% after more than 200 days after diagnosis. Spike antibodies remained elevated in 93.6% of unvaccinated children after more than 200 days after diagnosis. By April 2022, 408 (95.6%) children 12 years and older had received 2 or more vaccine doses, and 241 (61.6%) 5 to 11 year-old children had received 2 vaccine doses. At that time, all 685 vaccinated children had spike antibodies, compared with 94/176 (53.4%) of unvaccinated children. Conclusions: In our population, after the first peak of Omicron variant infections and introduction of COVID-19 vaccines for children, all vaccinated children had SARS-CoV-2 spike antibodies, in contrast to 53.4% of unvaccinated children. It is not yet known whether a high level of seropositivity at a point in time indicates sustained population-level protection against SARS-CoV-2 transmission or severe COVID-19 outcomes in children.
Background: Monitoring safety outcomes following COVID-19 vaccination is critical for understanding vaccine safety especially when used in key populations such as elderly persons age 65 years and older who can benefit greatly from vaccination. We present new findings from a nationally representative early warning system that may expand the safety knowledge base to further public trust and inform decision making on vaccine safety by government agencies, healthcare providers, interested stakeholders, and the public. Methods: We evaluated 14 outcomes of interest following COVID-19 vaccination using the US Centers for Medicare & Medicaid Services (CMS) data covering 30,712,101 elderly persons. The CMS data from December 11, 2020 through Jan 15, 2022 included 17,411,342 COVID-19 vaccinees who received a total of 34,639,937 doses. We conducted weekly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. Findings: Four outcomes met the threshold for a statistical signal following Pfizer-BioNTech vaccination including pulmonary embolism (PE; RR=1.54), acute myocardial infarction (AMI; RR=1.42), disseminated intravascular coagulation (DIC; RR=1.91), and immune thrombocytopenia (ITP; RR=1.44). After further evaluation, only the RR for PE still met the statistical threshold for a signal; however, the RRs for AMI, DIC, and ITP no longer did. No statistical signals were identified following vaccination with either the Moderna or Janssen vaccines. Interpretation: This early warning system is the first to identify temporal associations for PE, AMI, DIC, and ITP following Pfizer-BioNTech vaccination in the elderly. Because an early warning system does not prove that the vaccines cause these outcomes, more robust epidemiologic studies with adjustment for confounding factors, including age and nursing home residency, are underway to further evaluate these signals. FDA strongly believes the potential benefits of COVID-19 vaccination outweigh the potential risks of COVID-19 infection.
Mycobacterium-w (Mw), was shown to boost adaptive natural killer (ANK) cells and protect against COVID-19 during the first wave of the pandemic. As a follow-up of the trial, 50 healthcare workers (HCW) who had received Mw in September 2020 and subsequently received at least one dose of ChAdOx1 nCoV-19 vaccine (Mw+ChAdOx1 group) were monitored for symptomatic COVID-19, during a major outbreak with the delta variant of SARS-CoV-2 (April-June, 2021), along with 201 HCW receiving both doses of the vaccine without Mw (ChAdOx1 group). Despite 48% having received just a single dose of the vaccine in Mw+ChAdOx1 group, only 2 had mild COVID-19, compared to 36 infections in the ChAdOx1 group (HR-0.46, p=0.009). Transcriptomic studies revealed an enhanced adaptive NK cell-dependent ADCC in the Mw+ChAdOx1 group, along with downregulation of TLR2-MYD88 pathway and concomitant attenuation of downstream inflammatory pathways. This might have resulted in robust protection during the pandemic with the delta variant.
Background: Our objective was to evaluate the real world effectiveness of nirmatrelvir/ritonavir to prevent severe COVID-19 while Omicron and its subvariants predominate. Methods: We conducted a population based cohort study in Ontario, Canada including all residents >17 years of age who tested positive for SARS-CoV-2 by PCR between 4 April and 31 August 2022. We compared nirmatrelvir/ritonavir treated patients to unexposed patients and measured the primary outcome of hospitalization or death from COVID-19, and a secondary outcome of death 1-30 days. We used weighted logistic regression to calculate weighted odds ratios (wOR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. Results: The final cohort included 177,545 patients with 8,876 (5.0%) exposed and 168,669 (95.0%) unexposed individuals. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. Hospitalization or death within 30 days was lower in the nirmatrelvir/ritonavir treated group compared to unexposed individuals (2.1% vs 3.7%, wOR 0.56; 95%CI, 0.47-0.67). In the secondary analysis, the relative odds of death was also significantly reduced (1.6% vs 3.3%, wOR 0.49; 95%CI, 0.39-0.62). The number needed to treat to prevent one case of severe COVID-19 was 62 (95%CI 43 to 80). Findings were similar across strata of age, DDIs, vaccination status, and comorbidities. Interpretation: Nirmatrelvir/ritonavir was associated with significantly reduced risk of hospitalization and death from COVID-19 in this observational study, supporting ongoing use of this therapeutic to treat patients with mild COVID-19 at risk for severe disease.
Background: Post-acute sequelae of SARS-Co-V-2 infection (PASC) is associated with worsening diabetes trajectory. It is unknown whether PASC in children with type 1 diabetes (T1D) manifests as worsening diabetes trajectory. Objective: To explore the association between SARS-CoV-2 infection (COVID-19) and T1D-related healthcare utilization (for diabetic ketoacidosis [DKA] or severe hypoglycemia [SH]) or Hemoglobin (Hb) A1c trajectory. Methods: We included children <21 years with T1D and ≥1 HbA1c prior to cohort entry, which was defined as COVID-19 (positive diagnostic test or diagnosis code for COVID-19, multisystem inflammatory syndrome in children, or PASC) or a randomly selected negative test for those who were negative throughout the study period (Broad Cohort). A subset with ≥1 HbA1c value from 28-275 days after cohort entry (Narrow Cohort) was included in the trajectory analysis. Propensity score-based matched cohort design followed by weighted Cox regression was used to evaluate the association of COVID-19 with healthcare utilization >28 days after cohort entry. Generalized estimating equation models were used to measure change in HbA1c in the Narrow cohort. Results: From 03/01/2020-06/22/2022, 2,404 and 1,221 youth met entry criteria for the Broad and Narrow cohorts, respectively. The hazard ratio for utilization was (HR 1.45 [95%CI,0.97,2.16]). In the Narrow Cohort, the rate of change (slope) of HbA1c increased 91-180 days after cohort entry for those with COVID-19 (0.138 vs. -0.002, p=0.172). Beyond 180 days, greater declines in HbA1c were observed in the positive cohort (-0.104 vs. 0.008 per month, p=0.024). Conclusion: While a trend towards worse outcomes following COVID-19 in T1D patients was observed, these findings were not statistically significant. Continued clinical monitoring of youth with T1D following COVID-19 is warranted.
Background & Aims: Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019, commonly involving the gastrointestinal tract. Some children with MIS-C undergo appendectomy before the final diagnosis. There are several hypotheses explaining pathomechanism of MIS-C, with the central role of the viral antigen persistence in the gut, associated with lymphocyte exhaustion and immune system dysregulation. We aimed to examine appendectomy specimens obtained from MIS-C patients and analyze the pathological features of the disease and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in the appendix. Methods: In this cross-sectional study we included 21 children with MIS-C who underwent appendectomy before the final diagnosis. MIS-C patients were recruited from the Polish national registry of inflammatory syndromes in children. The control group included 21 sex- and age-matched children with acute appendicitis (AA) unrelated to SARS-CoV-2 infection. Histological evaluation involved hematoxylin and eosin staining and immunohistochemical identification of lymphocyte subpopulations, programmed cell death protein 1, and SARS-CoV-2 nucleocapsid antigen. Results: Appendices of MIS-C patients lacked neutrophilic infiltrate of muscularis propria typical for AA (14 vs 95%, p<0.001). The proportion of CD20+ to CD5+ cells was higher in patients with MIS-C (p 0.04), as well as the proportion of CD4+ to CD8+ (p <0.001). We found no proof of SARS-CoV-2 antigen presence, nor lymphocyte exhaustion, in the appendices of MIS-C patients. Conclusions: Our findings describe pathomorphological features of the appendix in MIS-C and argue against the central role of SARS-CoV-2 persistence in the gut and concomitant lymphocyte exhaustion as the major triggers of MIS-C.
Long Covid – the disease encompassing the post-acute sequelae of SARS-CoV-2 (PASC) – affects millions of people around the world. Prevention of PASC is an urgent public health priority. In this work, we aimed to examine whether treatment with nirmatrelvir in the acute phase of COVID-19 is associated with reduced risk of post-acute sequelae. We used the healthcare databases of the US Department of Veterans Affairs to identify users of the health system who had a SARS-CoV-2 positive test between March 01, 2022 and June 30, 2022, were not hospitalized on the day of the positive test, had at least 1 risk factor for progression to severe COVID-19 illness and survived the first 30 days after SARS-CoV-2 diagnosis. We identify those who were treated with oral nirmatrelvir within 5 days after the positive test (n=9217) and those who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection (control group, n= 47,123). Inverse probability weighted survival models were used to estimate the effect of nirmatrelvir (versus control) on a prespecified panel of 12 post-acute COVID-19 outcomes and reported as hazard ratio (HR) and absolute risk reduction (ARR) in percentage at 90 days. Compared to the control group, treatment with nirmatrelvir was associated with reduced risk of PASC (HR 0.74 95% CI (0.69, 0.81), ARR 2.32 (1.73, 2.91)) including reduced risk of 10 of 12 post-acute sequelae in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (deep vein thrombosis, and pulmonary embolism), fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath. Nirmatrelvir was also associated with reduced risk of post-acute death (HR 0.52 (0.35, 0.77), ARR 0.28 (0.14, 0.41)), and post-acute hospitalization (HR 0.70 (0.61, 0.80), ARR 1.09 (0.72, 1.46)). Nirmatrelvir was associated with reduced risk of PASC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection. In sum, our results show that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test was associated with reduced risk of PASC regardless of vaccination status and history of prior infection. The totality of findings suggests that treatment with nirmatrelvir during the acute phase of COVID-19 reduces the risk of post-acute adverse health outcomes.
Background: Limited data exist regarding longer-term antibody responses following three-dose COVID-19 vaccination, and the impact of a first SARS-CoV-2 infection during this time, in people living with HIV (PLWH) receiving suppressive antiretroviral therapy (ART). We quantified wild-type-(WT), Omicron BA.1- and Omicron BA.5-specific responses up to six months post-third dose in 64 PLWH and 117 controls who remained COVID-19-naive or experienced their first SARS-CoV-2 infection during this time. Design: Longitudinal observational cohort. Methods: We quantified WT- and Omicron-specific Anti-Spike receptor-binding domain IgG concentrations, ACE2 displacement activities and live virus neutralization at one, three and six months post-third vaccine dose. Results: Third doses boosted all antibody measures above two-dose levels, but BA.1-specific responses remained significantly lower than WT-specific ones, with BA.5-specific responses lower still. Serum IgG concentrations declined at similar rates in COVID-19-naive PLWH and controls post-third dose (median WT- and BA.1-specific half-lives were between 66-74 days for both groups). Antibody function also declined significantly yet comparably between groups: six months post-third dose, BA.1-specific neutralization was undetectable in >80% of COVID-19 naive PLWH and >90% of controls. Breakthrough SARS-CoV-2 infection boosted antibody concentrations and function significantly above vaccine-induced levels in both PLWH and controls, though BA.5-specific neutralization remained significantly poorer than BA.1 even post-breakthrough. Conclusions: Following three-dose COVID-19 vaccination, antibody response durability in PLWH receiving ART is comparable to controls. PLWH also mounted strong responses to breakthrough infection. Due to temporal response declines however, COVID-19-naive individuals, regardless of HIV status, would benefit from a fourth dose within 6 months of their third.
The research around the public9s usage of masks to prevent the spread of COVID-19 is developing quickly. In this work, we analyzed data from 50 nations to assess the long-term effectiveness of mask policies with different levels using the Poisson regression model and generalized linear mixed model. Over the long term, stricter obligatory mask regulations were linked to more stable patterns and slower increases in Covid-19 case occurrences. The mitigation of disease transmission by mask policies was shown to have substantial major impacts throughout the entire year of 2020, whereas the incidence of illness displays increasing trends over time under various policies. When compared to no mask policy deployment, mask policies might reduce incidence growth by 13.5% to 17.8%, although the incidence under every policy climbed 1.5% to 1.9% on average every ten days. The mask policy is effective in controlling illness, according to the bulk of the data shown above. This result confirms the mask policy9s importance as a governing approach in the context of the worldwide pandemic.
COVID-19 arrived in the United States in early 2020, with cases quickly being reported in many states including Pennsylvania. Many statistical models have been proposed to understand the trends of the COVID-19 pandemic and factors associated with increasing cases. While Poisson regression is a natural choice to model case counts, this approach fails to account for correlation due to spatial locations. Being a contagious disease and often spreading through community infections, the number of COVID-19 cases are inevitably spatially correlated as locations neighboring counties with a high COVID-19 case count are more likely to have a high case count. In this analysis, we combine generalized estimating equations for Poisson regression, a popular method for analyzing correlated data, with a semivariogram, to model daily COVID-19 case counts in 67 Pennsylvania counties between March 20, 2020 to January 23, 2021 in order to study infection dynamics during the beginning of the pandemic. We use a semivariogram that describes the spatial correlation as a function of the distance between two counties as the working correlation. We further incorporate a zero-inflated model in our spatial GEE to accommodate excess zeros in reported cases due to logistical challenges associated with disease monitoring. By modeling time-varying holiday covariates, we estimated the effect of holiday timing on case count. Our analysis showed that the incidence rate ratio was significantly greater than one, 6-8 days after a holiday suggesting a surge in COVID-19 cases approximately one week after a holiday.
Background The COVID-19 pandemic has put tremendous pressure on hospital resources around the world. Forecasting demand for healthcare services is important generally, but crucial in epidemic contexts, both to facilitate resource planning and to inform situational awareness. There is abundant research on methods for predicting the spread of COVID-19 and even the arrival of COVID-19 patients to hospitals emergency departments. This study builds on that work to propose a hybrid tool, combining a stochastic Markov model and a discrete event simulation model to dynamically predict hospital admissions and total daily occupancy of hospital and ICU beds. Methods The model was developed and validated at San Juan de Alicante University Hospital from 10 July 2020 to 10 January 2022 and externally validated at Hospital Vega Baja. An admissions generator was developed using a stochastic Markov model that feeds a discrete event simulation model in R. Positive microbiological SARS-COV-2 results from the health department’s catchment population were stratified by patient age to calculate the probabilities of hospital admission. Admitted patients follow distinct pathways through the hospital, which are simulated by the discrete event simulation model, allowing administrators to estimate the bed occupancy for the next week. The median absolute difference (MAD) between predicted and actual demand was used as a model performance measure. Results With respect to the San Juan hospital data, the admissions generator yielded a MAD of 6 admissions/week (interquartile range [IQR] 2-11). The MAD between the tool’s predictions and actual bed occupancy was 20 beds/day (IQR 5-43), or 5% of the hospital beds. The MAD between the intensive care unit (ICU)’s predicted and actual occupancy was 4 beds/day (IQR 2-7), or 25% of the beds. When the model was further evaluated with data from Hospital Vega Baja, the admissions generator showed a MAD of 2.42 admissions/week (IQR 1.02-7.41). The MAD between the tools’ predictions and the actual bed occupancy was 18 beds/day (IQR 19.57-38.89), or 5.1% of the hospital beds. For ICU beds, the MAD was 3 beds/day (IQR 1-5), or 21.4% of the ICU beds. Conclusion Predictions of hospital admissions, ward beds, and ICU occupancy for COVID-19 patients were very useful to hospital managers, allowing early planning of hospital resource allocation.
Using a Community-level Just-in-Time Adaptive Intervention to Address COVID-19 Testing Disparities - Condition: COVID-19
Interventions: Behavioral: Multi-Level Multi-Component Intervention (MLI); Behavioral: Community Just-In-Time Adaptive Intervention (Community JITAI)
Sponsors: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)
Active, not recruiting
Safety and Efficacy of Medications COVID-19 - Condition: Severe Covid-19
Intervention: Drug: Oral bedtime melatonin
Sponsor: Hospital San Carlos, Madrid
Completed
Use of Multiple Doses of Convalescent Plasma in Mechanically Intubated Patients With COVID-19 - Condition: COVID-19
Intervention: Biological: Multiple doses of anti-SARS-CoV-2 Convalescent Plasma
Sponsors: Hospital Regional Dr. Rafael Estévez; Complejo Hospitalario Dr. Arnulfo Arias Madrid; Hospital Santo Tomas; Hospital Punta Pacífica, Pacífica Salud; Insituto Conmemorativo Gorgas de Estudios para la Salud; Sociedad Panameña de Hematología; Institute of Scientific Research and High Technology Services (INDICASAT AIP); University of Panama; Sistema Nacional de Investigación de Panamá
Completed
Examining How a Facilitated Self-Sampling Intervention and Testing Navigation Intervention Influences COVID-19 Testing - Condition: COVID-19
Interventions: Behavioral: Facilitated Self-Sampling Intervention (FSSI); Behavioral: Testing Navigation Intervention (TNI).; Behavioral: Control
Sponsors: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)
Not yet recruiting
A Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older - Condition: COVID-19
Interventions: Biological: EuCorVac-19; Biological: ChAdOx1
Sponsor: EuBiologics Co.,Ltd
Recruiting
Open Multicenter Study for Assessment of Efficacy and Safety of Molnupiravir in Adult Patients With COVID-19 - Condition: COVID-19
Interventions: Drug: Molnupiravir (Esperavir); Drug: Standard of care
Sponsor: Promomed, LLC
Completed
Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population - Condition: COVID-19
Interventions: Drug: nirmatrelvir/ritonavir; Drug: Standard of care
Sponsors: Promomed, LLC; Sponsor GmbH
Completed
Study Evaluating GS-5245 in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness - Condition: COVID-19
Interventions: Drug: GS-5245; Drug: GS-5245 Placebo
Sponsor: Gilead Sciences
Recruiting
Effects of Respiratory Muscle Training in Individuals With Long-term Post-COVID-19 Symptoms - Conditions: Covid19; Post-acute COVID-19 Syndrome
Interventions: Other: Inspiratory + expiratory muscle training group; Other: Inspiratory + expiratory muscle training sham group; Other: Exercise training program
Sponsors: Universidad Complutense de Madrid; Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid
Recruiting
Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) Phase III Clinical Trial - Conditions: COVID-19; Coronavirus Infections
Interventions: Biological: LIBP-Rec-Vaccine; Biological: BIBP-Rec-Vaccine; Biological: placebo
Sponsors: National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co Ltd.
Not yet recruiting
A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza - Conditions: Influenza, Human; COVID-19
Interventions: Biological: bivalent BNT162b2 (original/Omi BA.4/BA.5); Biological: qIRV (22/23); Biological: QIV
Sponsors: BioNTech SE; Pfizer
Not yet recruiting
Study to Evaluate Safety, Tolerability, Efficacy and Pharmacokinetics of ASC10 in Mild to Moderate COVID-19 Patients - Condition: SARS CoV 2 Infection
Interventions: Drug: ASC10; Drug: Placebo
Sponsor: Ascletis Pharmaceuticals Co., Ltd.
Not yet recruiting
A Phase I/II Study of GLB-COV2-043 as a COVID-19 Vaccine Booster - Condition: COVID-19
Interventions: Drug: GLB-COV2-043; Drug: BNT162b2/COMIRNATY®
Sponsor: GreenLight Biosciences, Inc.
Not yet recruiting
Safety and Efficacy of Intranasal Administration of Avacc 10 Vaccine Against COVID-19 in Healthy Volunteers - Condition: COVID-19
Interventions: Biological: Avacc 10; Combination Product: Outer Membrane Vesicles (OMV) : OMV alone in vehicle; Other: Placebo
Sponsors: Intravacc B.V.; Novotech (Australia) Pty Limited
Not yet recruiting
The Phase Ⅱ/Ⅲ Trial of LYB001 - Condition: COVID-19
Interventions: Biological: LYB001; Biological: Placebo
Sponsor: Yantai Patronus Biotech Co., Ltd.
Not yet recruiting
Reduced circulating FABP2 in patients with moderate to severe COVID-19 may indicate enterocyte functional change rather than cell death - The gut is of importance in the pathology of COVID-19 both as a route of infection, and gut dysfunction influencing the severity of disease. Systemic changes caused by SARS-CoV-2 gut infection include alterations in circulating levels of metabolites, nutrients and microbial products which alter immune and inflammatory responses. Circulating plasma markers for gut inflammation and damage such as zonulin, lipopolysaccharide and β-glycan increase in plasma along with severity of disease. However,…
Generation of APN-chimeric gene-edited pigs by CRISPR/Cas9-mediated knock-in strategy - The prevalence of porcine enteric coronaviruses (PECs), including transmissible gastroenteritis virus (TGEV), swine acute diarrhea syndrome coronavirus (SADS-CoV), porcine delta coronavirus (PDCoV), and porcine epidemic diarrhea virus (PEDV), poses a serious threat to animal and public health. Here, we aimed to further optimize the porcine aminopeptidase N (pAPN) gene editing strategy to explore the balance between individual antiviral properties and the biological functions of pAPN in pigs….
SCUBE1 is associated with thrombotic complications, disease severity, and in-hospital mortality in COVID-19 patients - CONCLUSIONS: SCUBE1 may be one of the major determinants of thrombotic complications, which is an increased cause of mortality and morbidity in COVID-19 patients so inhibition of this peptide may be among the therapeutic targets in patients with COVID-19.
SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia - CONCLUSIONS: Coronaviruses, including SARS-CoV-2, cause AEC apoptosis, mitochondrial fission, and bioenergetic impairment. SARS-CoV-2 also suppresses HPV by targeting mitochondria. This mitochondriopathy is replicated by transduction with SARS-CoV-2 proteins, indicating a mechanistic role for viral-host mitochondrial protein interactions. Mitochondriopathy is a conserved feature of coronaviral pneumonia that may exacerbate hypoxemia and constitutes a therapeutic target.
An improved Fuzzy based GWO algorithm for predicting the potential host receptor of COVID-19 infection - Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has infected millions worldwide. SARS-CoV-2 spike protein uses Angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) for entering and fusing the host cell membrane. However, interaction with spike protein receptors and protease processing are not the only factors determining coronaviruses’ entry. Several proteases mediate the entry of SARS-CoV-2 virus into…
Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin - The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves dysregulations of iron metabolism, and although the mechanism of this pathology is not yet fully understood, correction of iron metabolism pathways seems a promising pharmacological target. The previously observed effect of inhibiting SARS-CoV-2 infection by ferristatin II, an inducer of transferrin receptor 1 (TfR1) degradation, prompted the study of competition between Spike protein and TfR1…
Rational design of the zonulin inhibitor AT1001 derivatives as potential anti SARS-CoV-2 - Although vaccines are greatly mitigating the worldwide pandemic diffusion of SARS-Cov-2, therapeutics should provide many distinct advantages as complementary approach to control the viral spreading. Here, we report the development of new tripeptide derivatives of AT1001 against SARS-CoV-2 M^(pro). By molecular modeling, a small compound library was rationally designed and filtered for enzymatic inhibition through FRET assay, leading to the identification of compound 4. X-ray crystallography…
Recent advances in understanding spleen tyrosine kinase (SYK) in human biology and disease, with a focus on fostamatinib - Spleen tyrosine kinase (SYK) is an important regulatory molecule of signal transduction pathways involved in the pathogenesis of autoimmune diseases such as immune thrombocytopenia (ITP), and the SYK-signaling pathway has emerged as a potential target for the treatment of numerous diseases. The aim of this narrative review is to summarize the biological properties of SYK and its involvement in disease pathways, provide an update on SYK inhibitors in the treatment of ITP, and consider other…
Mechanism of N-0385 blocking SARS-CoV-2 to treat COVID-19 based on molecular docking and molecular dynamics - CONCLUSION: The mechanism of N-0385 treatment COVID-19 was investigated by molecular docking and molecular dynamics simulation. We speculated that N-0385 may not only inhibit SARS-CoV-2 invasion directly by acting on TMPRSS2, ACE2 and DPP4, but also inhibit the immune recognition process and inflammatory response by regulating TLR7, NLRP3 and IL-10 to prevent SARS-CoV-2 invasion. Therefore, these results suggested that N-0385 may act through multiple targets to reduce SARS-CoV-2 infection and…
Bovine lactoferrin inhibits SARS-CoV-2 and SARS-CoV-1 by targeting the RdRp complex and alleviates viral infection in the hamster model - Breast milk has been found to inhibit coronavirus infection, while the key components and mechanisms are unknown. We aimed to determine the components that contribute to the antiviral effects of breastmilk and explore their potential mechanism. Lactoferrin (Lf) and milk fat globule membrane (MFGM) inhibit SARS-CoV-2 related coronavirus GX_P2V and SARS-CoV-2 trVLP in vitro and block viral entry into cells. We confirmed that bovine lactoferrin (bLf) blocked the binding between human…
Constructing Janus Microsphere Membranes for Particulate Matter Filtration, Directional Water Vapor Transfer, and High-Efficiency Broad-Spectrum Sterilization - Commercial masks have significant drawbacks, including low water vapor transmission efficiency and limited ability to inhibit harmful microorganisms, whereas in this contribution, a series of Janus microsphere membranes are developed with hierarchical structures by quenching and crystallizing 12-hydroxystearic acid and halicin layer-by-layer on a polypropylene non-woven fabric, laminating them with hydrophilic cotton fibers in a one-pot process, and further demonstrate the potential of this…
Management of Severe and Critical COVID-19 Infection with Immunotherapies - Following the reduction in mortality demonstrated by dexamethasone treatment in severe COVID-19, many targeted immunotherapies have been investigated. Thus far, inhibition of IL-6 and JAK pathways have the most robust data and have been granted Emergency Use Authorization for treatment of severe disease. However, it must be noted that critically ill patients comprised a relatively small proportion of most of the trials of COVID-19 therapeutics, despite bearing a disproportionate burden of…
Topoisomerase 3b is dispensable for replication of a positive-sense RNA virus–murine coronavirus - A recent study demonstrated that a DNA-RNA dual-activity topoisomerase complex, TOP3B-TDRD3, is required for normal replication of positive-sense RNA viruses, including several human flaviviruses and coronaviruses; and the authors proposed that TOP3B is a target of antiviral drugs. Here we examined this hypothesis by investigating whether inactivation of Top3b can inhibit the replication of a mouse coronavirus, MHV, using cell lines and mice that are inactivated of Top3b or Tdrd3. We found that…
The urgency of strengthening health information to support public perception and involvement in the COVID-19 vaccine - CONCLUSIONS: Strengthening positive information can alter the sense of community vulnerability, making it a driving force for participation in the COVID-19 vaccine campaign. This finding is an appropriate strategy to expand the reach and resolve public doubts about accepting the vaccine.
S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters - In parallel with vaccination, oral antiviral agents are highly anticipated to act as countermeasures for the treatment of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oral antiviral medication demands not only high antiviral activity, but also target specificity, favorable oral bioavailability, and high metabolic stability. Although a large number of compounds have been identified as potential inhibitors of SARS-CoV-2…