Effective public-health measures and vaccination campaigns against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against the ectodomain and the receptor-binding domain of the spike protein as well as the nucleocapsid protein of SARS-CoV-2. We used TRABI for continuous seromonitoring of hospital patients and healthy blood donors (n=729222) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). Seroprevalence peaked in May 2020 and rose again in November 2020 in both cohorts. Validations of results included antibody diffusional sizing and Western Blotting. Using an extended Susceptible-Exposed-Infectious-Removed model, we found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020 in the population of the canton of Zurich. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19 and up to the timepoint of survey participation. Crucially, we found no evidence for a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae.
Background: Segregation of unvaccinated people from public spaces has been a novel and controversial COVID-era public health practice in many countries. Models have been used to explore potential epidemiological impacts of vaccination-status-based segregation, however existing models do not realistically represent the segregation because they neglect its effect on decreasing or increasing the contact frequencies of the segregated individuals. We systematically investigate how including the effect of segregation on contact frequencies changes predicted epidemiological outcomes. Methods: We describe a susceptible-infectious-recovered (SIR) two-population model for vaccinated and unvaccinated groups of individuals that transmit an infectious disease by pairwise person-to-person contact. The degree of segregation between the two groups, ranging from no segregation to complete segregation, is implemented using the like-to-like mixing approach developed by Garnett and Anderson (1996) for sexually transmitted diseases and recently applied to SARS-CoV-2 transmission and vaccination (Fisman et al., 2022). The model allows the contact frequencies for individuals in the two groups to be different and to depend, with variable strength, on the degree of segregation. Results: Model predictions for a broad range of model assumptions and respiratory-disease epidemiological parameters are calculated to examine the effects of segregation. Segregation can either increase or decrease the attack rate among the vaccinated, depending on the type of segregation (whether isolating or compounding), and on the contagiousness of the disease. For diseases with relatively low contagiousness, segregation can cause an attack rate in the vaccinated, which does not occur without segregation. Interpretation: There is no blanket epidemiological advantage to implementing segregation, either for the vaccinated or the unvaccinated. Negative epidemiological consequences can occur for both groups.
Maternal immune responses during pregnancy protect the growing fetus by clearing infection, preventing its vertical transmission, and through transplacental transfer of protective immune mediators to the fetus. How maternal immune response balances SARS-CoV-2 antiviral responses with transplacental transfer of protection to the fetus remains unclear. Our study shows that upon SARS-CoV-2 maternal infection, neutralizing antibodies (NAbs) are infrequently detected in cord blood. We uncovered that this is due to impaired IgG-NAbs placental transfer in symptomatic infection and to the predominance of maternal SARS-CoV-2 NAbs of the IgA and IgM isotypes, which are prevented from crossing the placenta. Crucially, the decision between favoring maternal antiviral response or transplacental transfer of immune protection to the fetus appears to hinge on the balance between IL-6 and IL-10 induced by SARS-CoV-2 infection, decreasing or increasing transplacental transfer of IgG-NAbs, respectively. In addition, IL-10 inversely correlates with maternal NK cell frequency. Finally, we found that ongoing infection favored perinatal transfer of maternal NK cells, highlighting a maternal sponsored mechanism to protect the newborn from horizontal transmission of infection. Our data point to an evolutionary trade-off which at once optimizes maternal viral clearance and vertical transfer of immune protection during the more susceptible perinatal period.
Study Objective Tools proposed to triage acuity in suspected COVID-19 in the ED have been derived and validated in higher-income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa. Methods An observational cohort study using routinely collected data from EDs across the Western Cape, from the 27th of August 2020 to 11th March 2022 was conducted to assess performance of the PRIEST tool, NEWS2, TEWS, the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS in suspected COVID-19. The primary outcome was death or ICU admission. Results Of 446,084 patients, 15,397 patients (3.45%, 95% CI:34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST tool algorithm identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.47 (NEWS2) to 0.65 (PRIEST tool). Use of the tools at recommended thresholds would have more than doubled admissions with only a 0.01% reduction in false negative triage. Conclusion Use of the PRIEST score, NEWS2 and PMEWS at a threshold of a point higher would achieve similar accuracy to current clinical admission decision, with possible gains in transparency and speed of decision-making.
Background<br />Worldwide, most colorectal cancer screening programmes were paused at the start of the COVID-19 pandemic, whilst the Danish faecal immunochemical test (FIT)-based programme continued without pausing. We examined colorectal cancer screening participation and compliance with subsequent colonoscopy in Denmark throughout the pandemic.<br /><br />Methods<br />We used data from the Danish Colorectal Cancer Screening Database among individuals aged 50-74 years old invited to participate in colorectal cancer screening from 2018-2021 combined with population-wide registries. Using a generalised linear model, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) of colorectal cancer screening participation within 90 days since invitation and compliance with colonoscopy within 60 days since a positive FIT test during the pandemic in comparison with the previous years adjusting for age, month and year of invitation.<br /><br />Results<br />Altogether, 3,133,947 invitations were sent out to 1,928,725 individuals and there were 94,373 positive FIT tests (in 92,848 individuals) during the study period. Before the pandemic, 60.7% participated in screening within 90 days. A minor reduction in participation was observed at the start of the pandemic (PR=0.95; 95% CI: 0.94-0.96 in pre-lockdown and PR=0.85; 95% CI: 0.85-0.86 in 1st lockdown) corresponding to a participation rate of 54.9% during pre-lockdown and 53.0% during 1st lockdown. This was followed by a 5-10% increased participation in screening corresponding to a participation rate of up to 64.9%. The largest increase in participation was observed among 55-59 year olds, individuals living alone or cohabiting and immigrants. The compliance with colonoscopy within 60 days was 89.9% before the pandemic. A slight reduction was observed during 1st lockdown (PR=0.96; 95% CI: 0.93-0.98), where after it resumed to normal levels.<br /><br />Conclusions<br />Participation in the Danish FIT-based colorectal cancer screening programme and subsequent compliance to colonoscopy after a positive FIT result was only slightly affected by the COVID-19 pandemic.<br /><br />Funding<br />The study was funded by the Danish Cancer Society Scientific Committee (grant number R321- A17417) and the Danish regions.
Importance: Individuals at increased risk for severe outcomes from COVID-19, due to compromised immunity or other risk factors, would benefit from objective measures of vulnerability to infection based on prior infection and/or vaccination. We reviewed published data to identify a specific role and interpretation of SARS-CoV-2 spike-targeted serology testing for such individuals. We also provide real-world evidence of spike-targeted antibody test results, identifying the seronegativity rate across the United States from March 2021 through June 2022. Analysis of antibody test results were compared between post-transplant (ie, immunocompromised) and all other patients tested in the first half of 2022. Finally, specific recommendations are provided for an evidence-based and clinically useful interpretation of spike-targeted serology to identify vulnerability to infection and potential subsequent adverse outcomes. Observations: Decreased vaccine effectiveness among immunocompromised individuals is linked to correspondingly high rates of breakthrough infections. Evidence indicates that negative results on SARS-CoV-2 antibody tests are associated with increased risk for subsequent infection. Results from widely available, laboratory-based tests do not provide a direct measure of protection but appear to correlate well with the presence of surrogate pseudovirus-neutralizing antibodies. The results of SARS-CoV-2 semiquantitative tests have also been associated with vaccine effectiveness and the likelihood of breakthrough infection. The data suggest that “low-positive” results on semiquantitative SARS-CoV-2 spike-targeted antibody tests may help identify persons at increased relative risk for breakthrough infection leading to adverse outcomes. In an analysis of data from large national laboratories during the COVID-19 Omicron-related surge in 2022, results from SARS-CoV-2 spike-targeted antibody tests were negative in 16.6% (742/4459) of solid organ transplant recipients tested compared to only 11.0% (47,552/432,481) of the remaining tested population. Conclusions and Relevance: Standardized semiquantitative and quantitative SARS-CoV-2 spike-targeted antibody tests may provide objective information on risk of SARS-CoV-2 infection and associated adverse outcomes. This holds especially for high-risk populations, including transplant recipients, who demonstrate a relatively higher rate of seronegativity. The widespread availability of such tests presents an opportunity to refine risk assessment for individuals with suboptimal SARS-CoV-2 antibody levels and to promote effective interventions. Interim federal guidance would support physicians and patients while additional investigations are pursued.
Background<br />In contrast to most of the world, the cervical cancer screening programme continued in Denmark throughout the COVID-19 pandemic. We examined the cervical cancer screening participation during the pandemic in Denmark.<br /><br />Methods<br />We included all women aged 23-64 years old invited to participate in cervical cancer screening from 2015-2021 as registered in the Cervical Cancer Screening Database combined with population-wide registries. Using a generalised linear model, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) of cervical cancer screening participation within 90, 180 and 365 days since invitation during the pandemic in comparison with the previous years adjusting for age, year and month of invitation.<br /><br />Results<br />Altogether, 2,220,000 invited women (in 1,466,353 individuals) were included in the study. Before the pandemic, 36% of invited women participated in screening within 90 days, 54% participated within 180 days and 65% participated within 365 days. At the start of the pandemic, participation in cervical cancer screening within 90 days was lower (pre-lockdown PR=0.58; 95% CI: 0.56-0.59 and 1st lockdown PR=0.76; 95% CI: 0.75-0.77) compared with the previous years. A reduction in participation within 180 days was also seen during pre-lockdown (PR=0.89; 95% CI: 0.88-0.90) and 1st lockdown (PR=0.92; 95% CI: 0.91-0.93). Allowing for 365 days to participation, only a slight reduction (3%) in participation was seen with slightly lower participation in some groups (immigrants, low education and low income).<br /><br />Conclusions<br />The overall participation in cervical cancer screening was reduced during the early phase of the pandemic. However, the decline almost diminished with longer follow-up time.<br /><br />Funding<br />The study was funded by the Danish Cancer Society Scientific Committee (grant number R321- A17417) and the Danish regions.
The SARS-CoV-2 Omicron variant has challenged the control of the COVID-19 pandemic even in highly vaccinated countries. While a second booster of mRNA vaccines improved the immunity against SARS-CoV-2, the humoral and cellular responses induced by a second booster of an inactivated SARS-CoV-2 vaccine have not been studied. In the context of a phase 3 clinical study, we report that a second booster of CoronaVac increased the neutralizing response against the ancestral virus yet showed poor neutralization against the Omicron variant. Additionally, isolated PBMCs displayed equivalent activation of specific CD4+ T lymphocytes and IFN-γ production when stimulated with a mega-pool of peptides derived from the spike protein of the ancestral virus or the Omicron variant. In conclusion, a second booster dose of CoronaVac does not improve the neutralizing response against the Omicron variant compared with the first booster dose, yet it helps maintain a robust spike-specific CD4+ T cell response.
Background. The B.1.1.529 (Omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the fourth COVID-19 pandemic wave across the southern African region, including Malawi. The seroprevalence of SARS-CoV-2 antibodies and their association with epidemiological trends of hospitalisations and deaths are needed to aid locally relevant public health policy decisions. Methods. We conducted a population-based serosurvey from December 27, 2021 to January 17, 2022, in 7 districts across Malawi to determine the seroprevalence of SARS-CoV-2 antibodies. Primary sampling units (PSU) were selected using probability proportionate to the number of households based on the 2018 national census, followed by second-stage sampling units that were selected from listed households. A random systematic sample of households was selected from each PSU within the 7 districts. Serum samples were tested for antibodies against SARS-CoV-2 receptor binding domain using WANTAI SARS-CoV-2 Receptor Binding Domain total antibody commercial enzyme-linked immunosorbent assay (ELISA). We also evaluated COVID-19 epidemiologic trends in Malawi, including cases, hospitalizations and deaths from April 1, 2021 through April 30, 2022, collected using the routine national COVID-19 reporting system. Results. Serum samples were analysed from 4619 participants (57% female; 65% aged 14 to 50 years), of whom 1018 (22%) had received a COVID-19 vaccine. The overall assay-adjusted seroprevalence was 86.3% (95% confidence interval (CI), 85.1% to 87.5%). Seroprevalence was lowest among children <13 years of age (66%) and highest among adults 18 to 50 years of age (82%). Seroprevalence was higher among vaccinated compared to unvaccinated participants (96% vs. 77%; risk ratio, 6.65; 95% CI, 4.16 to 11.40). Urban residents were more likely to test seropositive than those living in rural settings (91% vs. 78%; risk ratio, 2.81; 95% CI, 2.20 to 3.62). National COVID-19 data showed that at least a two-fold reduction in the proportion of hospitalisations and deaths among the reported cases in the fourth wave compared to the third wave (hospitalization, 10.7% (95% CI, 10.2 to 11.3) vs 4.86% (95% CI, 4.52 to 5.23), p<0.0001; deaths, 3.48% (95% CI, 3.18 to 3.81) vs 1.15% (95% CI, 1.00 to 1.34), p<0.0001). Conclusion. We report reduction in proportion of hospitalisations and deaths from SARS-CoV-2 infections during the Omicron variant dominated wave in Malawi, in the context of high SARS-CoV-2 seroprevalence but low COVID-19 vaccination coverage. These findings suggest that COVID-19 vaccination policy in high seroprevalence settings may need to be amended from mass campaigns to targeted vaccination of at-risk populations.
Abstract Background: Neutralizing monoclonal antibody (mAb) treatment for COVID-19 prevents hospitalization and death but is underused, especially in racial/ethnic minority and rural populations. The study assessed mAbs community awareness and opportunities for improving equitable mAb access. Methods: A concurrent mixed methods study including surveys and focus groups with adults with high-risk conditions or their proxy decision-makers. Surveys and focus group guides addressed diffusion of innovation theory factors. Descriptive statistics and Fisher’s exact method was used to report and compare survey findings by race and ethnicity. Rapid qualitative methods were used for focus group analysis. Results: Surveys from 515 individuals (460 English, 54 Spanish, 1 Amharic), and 8 focus groups (6 English, 2 Spanish) with 69 diverse participants, all completed between June 2021 and January 2022. Most survey respondents (75%) had heard little or nothing about mAbs, but 95% would consider getting mAb treatment. Hispanic/Latino and Non-Hispanic People of Color (POC) reported less awareness, greater concern about an intravenous infusion, and less trust in mAb safety and effectiveness than White, Non-Hispanic respondents. Focus group themes included little awareness but high interest in mAb treatment and concerns about cost and access, especially for those facing access barriers such as lacking an established source of care and travel from rural communities. Focus groups revealed preferences for broad-reaching but tailored messaging strategies using multiple media and trusted community leaders. Conclusions: Despite unfamiliarity with mAb treatment, most respondents were willing to consider receiving mAbs or recommend mAbs to others. While mAb messaging should have broad reach “to everyone everywhere,” racial and geographic disparities in levels of awareness and trust about mAbs underscore the need for tailored messaging to promote equitable access. Care processes should address patient-level mAb barriers, such as transportation, insurance, or primary care access. COVID-19 treatment dissemination strategies should promote health equity.
A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19 - Condition: COVID-19
Interventions: Drug: SIM0417; Drug: Placebo
Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Not yet recruiting
Self-management of Post COVID-19 Syndrome Using Wearable Biometric Technology - Condition: COVID-19
Intervention: Other: Self-management of post COVID-19 respiratory outcomes
Sponsor: University of Manitoba
Not yet recruiting
Clinical Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients - Condition: COVID-19
Interventions: Drug: Casirivimab and Imdevimab Drug Combination; Drug: Remdesivir; Drug: Favipiravir
Sponsor: Mansoura University Hospital
Completed
The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines - Condition: COVID-19
Interventions: Biological: BCG (Bacillus Calmette-Guérin) vaccine; Other: Placebo
Sponsors: Oswaldo Cruz Foundation; University of Sao Paulo; Federal University of Juiz de Fora
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
Performance Evaluation of LumiraDx COVID-19 (SARS-CoV-2) Ag ULTRA Test (ASPIRE-2) - Condition: COVID-19
Interventions: Diagnostic Test: Nasal Swab; Diagnostic Test: Nasopharyngeal swab
Sponsor: LumiraDx UK Limited
Recruiting
Social Network Diffusion of COVID-19 Prevention for Diverse Criminal Legal Involved Communities - Condition: COVID-19
Interventions: Other: Education; Other: Motivational
Sponsor: University of Chicago
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
Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With COVID-19 - Condition: COVID-19 Infection
Interventions: Biological: Allogeneic umbilical cord mesenchymal stem cells; Biological: Controlled normal saline
Sponsor: Ever Supreme Bio Technology Co., Ltd.
Active, not recruiting
The Effects of a Sublingual Sprayable Microemulsion of Vitamin D on Inflammatory Markers in COVID-19 Patients - Conditions: COVID-19; Vitamin D Deficiency
Intervention: Dietary Supplement: Vitamin D 25 (OH) 12000 IU in the form of a sublingual sprayable microemulsion
Sponsor: Pauls Stradins Clinical University Hospital
Completed
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
UNAIR Inactivated COVID-19 Vaccine Phase 3 - Conditions: COVID-19 Pandemic; COVID-19 Vaccines
Interventions: Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg; Biological: CoronaVac Biofarma COVID-19 Vaccine
Sponsors: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia
Recruiting
Hydrogen-Oxygen Generator With Nebulizer for Rehabilitation Treatment of COVID-19 - Conditions: COVID-19; AMS-H-03; Hydrogen-oxygen Gas
Interventions: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Other: basic treatment
Sponsor: Shanghai Zhongshan Hospital
Recruiting
Clinical Trial of Jinzhen Oral Liquid in Treating Children With COVID-19 Infection - Conditions: COVID-19; Child, Only
Intervention: Drug: Jinzhen oral liquid or Jinhuaqinggan granules
Sponsor: The Affiliated Hospital of Qingdao University
Recruiting
Huashi Baidu Granule in the Treatment of Pediatric Patients With Mild Coronavirus Disease 2019 - Condition: Coronavirus Disease 2019
Interventions: Drug: Huashi Baidu granule; Drug: compound pholcodine oral solution
Sponsor: Shanghai Children’s Medical Center
Completed
Molecular mechanisms and therapeutic target of NETosis in diseases - Evidence shows that neutrophils can protect the host against pathogens in multiple ways, including the formation and release of neutrophil extracellular traps (NETs). NETs are web-like structures composed of fibers, DNA, histones, and various neutrophil granule proteins. NETs can capture and kill pathogens, including bacteria, viruses, fungi, and protozoa. The process of NET formation is called NETosis. According to whether they depend on nicotinamide adenine dinucleotide phosphate (NADPH),…
Reinforcement sensitivity theory may predict COVID-19 infection outcome and vulnerability - Research suggests that specific behavior patterns may be related with the outcome and vulnerability of a COVID-19 infection; nevertheless, much of this information has been obtained by means of psychological paradigms that are not based on research conducted using experimental designs. Thus, the purpose of the present study was to identify behavior patterns associated with COVID-19 outcome and vulnerability from the point of view of the Reinforcement Sensitivity Theory. A total of 464 college…
The Remarkable Roles of the Receptor for Advanced Glycation End Products (RAGE) and Its Soluble Isoforms in COVID-19: The Importance of RAGE Pathway in the Lung Injuries - The respiratory symptoms of acute respiratory distress syndrome (ARDS) in the coronavirus disease 2019 (COVID-19) patients is associated with accumulation of pre-inflammatory molecules such as advanced glycation end-products (AGES), calprotectin, high mobility group box family-1 (HMGB1), cytokines, angiotensin converting enzyme 2 (ACE2), and other molecules in the alveolar space of lungs and plasma. The receptor for advanced glycation end products (RAGEs), which is mediated by the…
Exposure to phenytoin associates with a lower risk of post-COVID cognitive deficits: a cohort study - Post-COVID cognitive deficits (often referred to as ‘brain fog’) are common and have large impacts on patients’ level of functioning. No specific intervention exists to mitigate this burden. This study tested the hypothesis, inspired by recent experimental research, that post-COVID cognitive deficits can be prevented by inhibiting receptor-interacting protein kinase. Using electronic health record data, we compared the cognitive outcomes of propensity score-matched cohorts of patients with…
Evaluation of a rapid semiquantitative lateral flow assay for the prediction of serum neutralizing activity against SARS-CoV-2 variants - CONCLUSIONS: The ichroma™ COVID-19 nAb assay, with appropriate variant cut-offs, can be useful for the monitoring of anti-SARS-CoV-2 immunization and may provide a rapid prediction of protection, especially in individuals with significant levels of NAbs.
Plant-derived compounds effectively inhibit the main protease of SARS-CoV-2: An in silico approach - The current coronavirus disease 2019 (COVID-19) pandemic, caused by the coronavirus 2 (SARS-CoV-2), involves severe acute respiratory syndrome and poses unprecedented challenges to global health. Structure-based drug design techniques have been developed targeting the main protease of the SARS-CoV-2, responsible for viral replication and transcription, to rapidly identify effective inhibitors and therapeutic targets. Herein, we constructed a phytochemical dataset of 1154 compounds using deep…
Discovery of novel potential inhibitors of TMPRSS2 and Mpro of SARS-CoV-2 using E-pharmacophore and docking-based virtual screening combined with molecular dynamic and quantum mechanics - The pandemic of coronavirus disease is caused by the SARS-CoV-2 which is considered a global health issue. The main protease of COVID 19 (Mpro) has an important role in viral multiplication in the host cell. Inhibiting Mpro is a novel approach to drug discovery and development. Also, transmembrane serine proteases (TMPSS2) facilitate viral activation by cleavage S glycoproteins, thus considered one of the essential host factors for COVID-19 pathogenicity. Computational tools were widely used to…
SARS-CoV-2 causes secretory diarrhea with an enterotoxin-like mechanism, which is reduced by diosmectite - CONCLUSIONS: SARS-CoV-2 induces calcium-dependent chloride secretion and oxidative stress without damaging intestinal epithelial structure. The effects are largely induced by the spike protein and are significantly reduced by diosmectite. SARS-CoV-2 should be added to the list of human enteric pathogens.
Quercetin against Emerging RNA Viral Diseases: Potential and Challenges for Translation - Because of higher adaptability and mutability, there is always a possibility for RNA viral disease outbreaks. There are no approved antivirals for the majority of RNA viruses including SARS-CoV-2, CHIKV, DENV, JEV, ZIKV, and EBOV. To treat these infections and to prepare for future epidemics there is a necessity to identify effective therapeutic strategies with broad-spectrum actions against RNA viruses. Unregulated inflammation is the major cause of the severity associated with these viral…
A nanomaterial targeting the spike protein captures SARS-CoV-2 variants and promotes viral elimination - The global emergency caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can only be solved with effective and widespread preventive and therapeutic strategies, and both are still insufficient. Here, we describe an ultrathin two-dimensional CuInP(2)S(6) (CIPS) nanosheet as a new agent against SARS-CoV-2 infection. CIPS exhibits an extremely high and selective binding capacity (dissociation constant (K(D)) < 1 pM) for the receptor binding domain of the spike…
Honghua extract mediated potent inhibition of COVID-19 host cell pathways - Honghua (Carthami flos) and Xihonghua (Croci stigma) have been used in anti-COVID-19 as Traditional Chinese Medicine, but the mechanism is unclear. In this study, we applied network pharmacology by analysis of active compounds and compound-targets networks, enzyme kinetics assay, signaling pathway analysis and investigated the potential mechanisms of anti-COVID-19. We found that both herbs act on signaling including kinases, response to inflammation and virus. Moreover, crocin likely has an…
Association between antidepressant use and ED or hospital visits in outpatients with SARS-CoV-2 - Antidepressants have previously been associated with better outcomes in patients hospitalized with COVID-19, but their effect on clinical deterioration among ambulatory patients has not been fully explored. The objective of this study was to assess whether antidepressant exposure was associated with reduced emergency department (ED) or hospital visits among ambulatory patients with SARS-CoV-2 infection. This retrospective cohort study included adult patients (N = 25 034) with a positive…
Aptamers targeting SARS-COV-2: a promising tool to fight against COVID-19 - SARS-CoV-2, the causative agent of COVID-19, remains among the main causes of global mortality. Although antigen/antibody-based immunoassays and neutralizing antibodies targeting SARS-CoV-2 have been successfully developed over the past 2 years, they are often inefficient and unreliable for emerging SARS-CoV-2 variants. Novel approaches against SARS-CoV-2 and its variants are therefore urgently needed. Aptamers have been developed for the detection and inhibition of several different viruses…
Evaluation of the active constituents of Nilavembu Kudineer for viral replication inhibition against SARS-CoV-2: An approach to targeting RNA-dependent RNA polymerase (RdRp) - The World Health Organization has declared the novel coronavirus (COVID-19) outbreak a global pandemic and emerging threat to people in the 21st century. SARS-CoV-2 constitutes RNA-Dependent RNA Polymerase (RdRp) viral proteins, a critical target in the viral replication process. No FDA-approved drug is currently available, and there is a high demand for therapeutic strategies against COVID-19. In search of the anti-COVID-19 compound from traditional medicine, we evaluated the active moieties…
Hesperetin as an anti-SARS-CoV-2 agent can inhibit COVID-19-associated cancer progression by suppressing intracellular signaling pathways - Hesperetin, an aglycone metabolite of hesperidin with high bioavailability, recently gained attention due to its anti-COVID-19 and anti-cancer properties. Multiple studies revealed that cancer patients are prone to experience a severe form of COVID-19 and higher mortality risk. In addition, studies suggested that COVID-19 can potentially lead to cancer progression through multiple mechanisms. This study proposes that hesperetin not only can be used as an anti-COVID-19 agent but also can reduce…