It is important to assess the extent to which the real-world effectiveness of marketed vaccines is consistent with that observed in the clinical trials, and to characterize how well vaccines prevent COVID-19 symptoms. We conducted a modified test-negative design (TND) to evaluate the RW effectiveness of three COVID-19 vaccines by leveraging data from an on-going, US community-based registry. Vaccine effectiveness was examined in two ways: considering cases who (1) tested positive for COVID-19 (695 cases, 1,786 controls) and who (2) tested positive with at least one moderate/severe COVID-19 symptom (165 cases, 2,316 controls). Any vaccination (full or partial) was associated with a 95% reduction in the odds of having a positive COVID-19 test [adjusted odds ratio (aOR) = 0.05 (95% confidence interval (CI): 0.04, 0.06)]. Full vaccination was associated with an aOR of 0.03 (95% CI: 0.03, 0.05) while partial vaccination had an aOR of 0.08 (95% CI: 0.06, 0.12). Any vaccination was associated with a 71% reduction in the odds of testing positive and having at least one moderate/severe symptom (aOR=0.29 (95% CI: 0.20, 0.40)). High effectiveness was observed across all three vaccine manufacturers both for prevention of positive COVID-19 test results and prevention of moderate/severe COVID-19 symptoms.
In this report, we use a detailed simulation model to assess and project the COVID-19 epidemic in Florida. The model is a data-driven, stochastic, discrete-time, agent based model with an explicit representation of people and places. Using the model, we find that the omicron variant wave in Florida is likely to cause many more infections than occurred during the delta variant wave. Due to testing limitations and often mild symptoms, however, we anticipate that omicron infections will be underreported compared to delta. We project that reported cases of COVID-19 will continue to grow significantly and peak in early January 2022, and that the number of reported COVID-19 deaths due to omicron may be 1/3 of the total caused by the delta wave.
Background. Two-dose mRNA vaccines reduce COVID-19 related hospitalization and mortality, but immune protection declines over time. As such, third vaccine doses are now recommended, particularly for older adults. We examined immune response durability up to 6 months after two vaccine doses, and immunogenicity after a third vaccine dose, in 151 adults ranging in age from 24 to 98 years. Methods. Specimens were collected from 81 healthcare workers (median age 41 years), 56 older adults (median 78 years) and 14 COVID-19 convalescent individuals (median 48 years), at one, three and six months following the second dose, and from 15 HCW, 28 older adults and 3 convalescent individuals at one month following a third dose. Binding antibodies to the SARS-CoV-2 spike receptor binding domain were quantified using a commercial immunoassay. Virus neutralizing activity was assessed using a live SARS-CoV-2 infection assay. Results. Compared to healthcare workers, older adults displayed ~0.3 log10 lower peak binding antibodies one month after the second dose (p<0.0001) and modestly faster rates of antibody decline thereafter (p=0.0067). A higher burden of chronic health conditions was independently associated with faster rates of antibody decline after correction for age, sociodemographic factors, and vaccine-related variables. Peak neutralizing activity was 4-fold lower in older adults one month after the second dose (p<0.0001) and became undetectable in the majority of individuals by six months. One month after a third dose, binding antibodies and neutralizing activities surpassed peak values achieved after two doses in both healthcare workers and older adults, and differences between these groups were no longer statistically significant. Compared to both naive groups, convalescent individuals displayed slower rates of binding antibody decline (p<0.006) and maintained higher neutralizing activity six months after the second dose. Conclusions. Immune responses to two-dose COVID-19 mRNA vaccines are overall weaker in older adults, and also decline more quickly over time, compared to younger adults. A third COVID-19 mRNA vaccine dose enhanced binding and neutralizing antibodies to levels higher than those observed after two vaccine doses, but the rate of decline of these responses should be monitored, particularly in older adults with a higher burden of chronic health conditions.
The SARS-CoV-2 Delta variant of concern (VOC), which has shown increased transmission compared with previous variants, emerged rapidly globally during the first half of 2021, and became one of the most widespread SARS-CoV-2 variants worldwide. We utilized total population data from 24,693 Danish households with 53,584 potential secondary cases to estimate household transmission of the Delta VOC in relation to vaccination status. We found that the vaccine effectiveness against susceptibility (VES) was 61% (95%-CI: 59-63) and that the vaccine effectiveness against transmissibility (VET) was 42% (95%-CI: 39-45). We also found that unvaccinated individuals with an infection exhibited a higher viral load (one third of a standard deviation) compared to fully vaccinated individuals with a breakthrough infection. Our results imply that vaccinations reduce susceptibility as well as transmissibility. The results are important for policy makers to select strategies for reducing transmission of SARS-CoV-2.
Abstract Background There has been an unprecedented global effort to produce safe and effective vaccines against SARS-CoV-2. However, production challenges, supply shortages and unequal global reach, together with an increased number of breakthrough infections due to waning of immunity and the emergence of new variants of concern (VOC), have prolonged the pandemic. To boost the immune response, several heterologous vaccination regimes have been tested and have shown increased antibody responses compared to homologous vaccination. Here we evaluated the effect of mRNA vaccine booster on immunogenicity in individuals who had been vaccinated with two doses of inactivated vaccines. Methods The levels of specific antibodies against the receptor-binding domain (RBD) of the spike protein from wild-type virus and the Beta, Delta and Omicron variants were measured in healthy individuals who had received two doses of homologous inactivated (BBIBP-CorV or CoronoVac) or mRNA (BNT162b2 or mRNA-1273) vaccines, and in donors who were given an mRNA vaccine boost after two doses of either vaccine. Pre-vaccinated healthy donors, or individuals who had been infected and subsequently received the mRNA vaccine were also included as controls. In addition, specific memory B and T cell responses were measured in a subset of samples. Results A booster dose of an mRNA vaccine significantly increased the level of specific antibodies that bind to the RBD domain of the wild-type (6-fold) and VOCs including Delta (8-fold) and Omicron (14-fold), in individuals who had previously received two doses of inactivated vaccines. The level of specific antibodies in the heterologous vaccination group was furthermore similar to that in individuals receiving a third dose of homologous mRNA vaccines or boosted with mRNA vaccine after natural infection. Moreover, this heterologous vaccination regime significantly enhanced the specific memory B and T cell responses. Conclusions Heterologous prime- boost immunization with inactivated vaccine followed by an mRNA vaccine boost markedly increased the levels of specific antibodies and B and T cell responses and may thus increase protection against emerging SARS-CoV-2 variants including Omicron.
BACKGROUND: Higher COVID-19 incidence and morbidity have been amply documented for US Black and Hispanic populations but not as clearly for other racial and ethnic groups. Efforts to elucidate the mechanisms underlying racial health disparities can be confounded by the relationship between race/ethnicity and socioeconomic status. OBJECTIVE: Examine race/ethnicity and social vulnerability effects on COVID-19 outcomes in the San Francisco Bay Area, an ethnically and socioeconomically diverse region. DESIGN: Retrospective cohort study. SETTING: Geocoded patient records from the University of California, San Francisco Health system between January 1, 2020 to December 31, 2020. PATIENTS: Patients who underwent polymerase chain reaction testing for COVID-19. EXPOSURES: Race/ethnicity and Social Vulnerability Index (SVI). MAIN MEASURES: COVID-19 test frequency, positivity, hospitalization rates, and mortality. KEY RESULTS: Higher social vulnerability, but not race/ethnicity, was associated with less frequent testing yet a higher likelihood of testing positive. Asian hospitalization rates (11.5%) were double that of White patients (5.4%) and exceeded the rates for Black (9.3%) and Hispanic (6.9%) groups. A modest relationship between higher hospitalization rates and increasing social vulnerability was evident only for White individuals. The Hispanic group had the lowest mean age at death and thus highest years of expected life lost due to COVID-19. CONCLUSIONS: COVID-19 outcomes were not consistently explained by greater socioeconomic vulnerability. Asian individuals showed disproportionately high rates of hospitalization regardless of socioeconomic status. Study of the San Francisco Bay Area population not only provides valuable insights into the differential contributions of race/ethnicity and social determinants of health to COVID-19 outcomes but also emphasizes that all racial groups have experienced the toll of the pandemic, albeit in different ways and to varying degrees.
In response to the ongoing COVID-19 pandemic and disparities of vaccination coverage in low-and middle-income countries, it is vital to adopt a widespread testing and screening programme, combined with contact tracing, to monitor and effectively control the infection dispersion in areas where medical resources are limited. This work presents a lab- on-a-chip platform, namely IFAST-CRISPR, as an affordable, rapid and high-precision molecular diagnostic means for SARS- CoV-2 detection. The herein proposed sample-to-answer platform integrates RNA extraction, amplification and CRISPR-Cas- based detection with lateral flow readout in one device. The microscale dimensions of the device containing immiscible liquids, coupled with the use of silica paramagnetic beads and GuHCl, streamline sample preparation, including RNA concentration, extraction and purification, in 15 min with minimal hands-on steps. By combining RT-LAMP with CRISPR- Cas12 assays targeting the nucleoprotein (N) gene, visual identification of ≥ 470 copies mL-1 genomic SARS-CoV-2 samples was achieved in 45 min, with no cross-reactivity towards HCoV-OC43 nor H1N1. On-chip assays showed the ability to isolate and detect SARS-CoV-2 from 1,000 genome copies mL-1 of replication-deficient viral particles in 1 h. This simple, affordable and integrated platform demonstrated a visual, faster, and yet specificity and sensitivity-comparable alternative to the costly gold-standard RT-PCR assay, requiring only a simple heating source. Further investigations on multiplexing and direct interfacing of the accessible Swan-brand cigarette filter for saliva sample collection could provide a complete work flow for COVID-19 diagnostics from saliva samples suitable for low-resource settings.
Objective: Easy and equitable access to testing is a cornerstone of the public health response to COVID-19. Currently in Australia, testing using Polymerase Chain Reaction (PCR) tests for COVID-19 is free-to-the-user, but the public purchase their own Rapid Antigen Tests (RATs). We conduct an economic analysis of government-funded RATs in Australia. Design: An interactive decision tree model was developed to compare one policy in which government-funded RATs are free-to-the-user, and one in which individuals purchase their own RATs. The decision tree represents RAT and PCR testing pathways for a cohort of individuals without COVID-19-like symptoms, to estimate the likelihood of COVID-19 positive individuals isolating prior to developing symptoms and the associated costs of testing, from a government perspective. Data sources: Test costs and detection rates were informed by published studies, other input parameter values are unobservable and uncertain, for which a range of scenario analyses are presented. Data synthesis: Assuming 10% prevalence of COVID-19 in a cohort of 10,000 individuals who would use government-funded RATs, the model estimates an additional 464 individuals would isolate early at a cost to the government of around $52,000. Scenario analyses indicate that the incremental cost per additional COVID-19 positive individual isolating with no symptoms remains at a few hundred dollars at 5% prevalence, rising to $2,052 at 1% prevalence. Conclusions: Based on the presented decision tree model, even only minor reductions in COVID-19 transmission rates due to early isolation would justify the additional costs associated with a policy of government-funded RATs.
The measures used to contain the COVID-19 pandemic caused severe disruption to the lives of children and adolescents, compromising their mental health and wellbeing. In this study we assessed the incidence rates of psychiatric diagnoses and drugs in Israeli adolescents before and during the COVID-19 pandemic. Analysis of health records data of over 200,000 12-17 years old adolescents identified a significant increase in all mental health diagnoses and most psychiatric drugs dispensation during the COVID-19 period compared to a corresponding pre-COVID period. A gender sub-analysis revealed that most of this increase was associated with adolescent girls. Girls exhibited increases of 68% in depression, 67% in eating disorders, 42% in anxiety and 29% in stress-related diagnoses during the COVID-19 period, which are significantly higher rates than those seen in boys and in the pre-COVID period. Sector sub- analysis showed that the increase was mainly in the general Jewish sector with almost no significant increases in the Arab and ultra-orthodox sectors. Our study highlights the mental health burden of Israeli adolescents during the pandemic and suggests that careful consideration should be given to it while deciding on measures to mitigate the pandemic.
The governance of COVID 19 in Lower and Middle-Income Countries (LMICs) is very critical for curbing its effects. However, it is unknown what governance strategies are adopted by Health Facility Governing Committees (HFGCs) s as a response to the pandemic. We employed an exploratory qualitative design to study the governance strategies adopted by HFGCs during the COVID19. Since COVID 19 is new, an inductive approach was used as it involves analyzing collected data with little or no predetermined theory for the study. A purposive sampling technique was employed in which multistage clustered sampling was used to select regions, councils, health facilities and respondents. In-depth interviews with HFGCs chairpersons and Focus Group Discussions with members of HFGCs were used to collect data. The data were analyzed based on the themes which emerged during data collection. We found five governance strategies that were found to be commonly adopted by many HFGCs which are financial allocation, re-planing, mobilization of resources, community sensitization and mobilization of stakeholders. however, these governance structures were not all adopted by all HFGCs. The HFGCs slowly adopted governance strategies in the times of COVID 19 pandemics because were unprepared. Despite being empowered by the Direct Health Facility Financing, still, the newest of the COVID 19 has been a challenge to many HFGCs. This calls for urgent capacity building for governance institutions on how to deal will pandemics in primary health facilities.
The accumulated numbers of COVID-19 cases and deaths per capita are important characteristics of the pandemic dynamics that may also indicate the effectiveness of quarantine, testing, vaccination, and treatment. The statistical analysis based on the number of cases per capita accumulated to the end of June 2021 showed no correlations with the volume of population, its density, and the urbanization level both in European countries and regions of Ukraine. The same result was obtained with the use of fresher datasets (as of December 23, 2021). The number of deaths per capita and per case may depend on the urbanization level. For European countries these relative characteristics decrease with the increase of the urbanization level. Opposite trend was revealed for the number of deaths per capita in Ukrainian regions.
Background: Long COVID is a post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection syndrome characterised by not recovering for several weeks or months following the acute episode. The effectiveness of COVID-19 vaccines against long-term symptoms of COVID19 is not well understood. We determined whether vaccination was associated with reporting long-term symptoms post-SARS-CoV-2 infection by comparing, among individuals previously infected with SARS-CoV-2, those who were vaccinated to those who were not, in terms of self-reported long-term symptoms. Methods: We invited individuals who were PCR tested for SARS-CoV-2 infection at participating hospitals between March 2020-June 2021 to fill an online questionnaire that included baseline demographics, details of their acute episode and information about symptoms they were currently experiencing. Using binomial regression, we compared vaccinated individuals with those unvaccinated in terms of self-reported symptoms post-acute infection. Results: Of 951 previously infected individuals who filled the survey 637(67%) were vaccinated. The most commonly reported symptoms were; fatigue (22%), headache (20%), weakness (13%), and persistent muscle pain (10%). After adjusting for follow-up time and baseline symptoms, fully vaccinated (2 or more doses) individuals were less likely than unvaccinated individuals to report any of these symptoms by 64%, 54%, 57%, and 68% respectively, (Risk ratios 0.36, 0.46, 0.43, 0.32, p<0.04 in the listed sequence). Conclusions: Vaccination with at least two doses of COVID-19 vaccine was associated with a substantial decrease in reporting the most common post-acute COVID19 symptoms. Our results suggest that, in addition to reducing the risk of acute illness, COVID-19 vaccination may have a protective effect against long COVID.
Abstract Objectives: Determine durability of protection by the three currently available COVID-19 vaccines in the United States (US) following primary vaccination against breakthrough infections, hospitalizations, and intensive care unit (ICU) admissions. Methods: Using claims and laboratory data covering 168 million lives, we conducted a matched case-control study with fully vaccinated individuals between January 1 and September 7, 2021. Odds ratios (OR) for developing outcomes in months two through six following full vaccination were estimated relative to the first month after full vaccination for each vaccine separately. Results: Evidence of waning protection against infections started in month 2 from vaccination for both BNT162b2 (OR [95% CI] in month 6+, 2.93 [2.72, 3.15]) and mRNA-1273 (OR [95% CI] in month 6+, 2.76 [2.51, 3.04]), and in month 4 for Ad26.COV2.S (OR [95% CI] in month 5+, 1.31 [1.18, 1.47]). Evidence of waning protection against hospitalization started in month 2 for BNT162b2 (OR [95% CI], 3.97 [3.26, 4.83] in month 6+) and in month 3 for mRNA-1273 (OR 95% CI, 1.66 [1.26, 2.19] in month 6+). There was no evidence of waning protection against hospitalization for Ad26.COV2.S (OR [95% CI], 1.25 [0.86, 1.80] in month 5+). No waning of protection was observed at any time for ICU admissions for all three vaccines. Conclusions: Following primary vaccination, all three vaccines showed strong and durable protection against ICU admissions. Ad26.COV2.S showed a more durable level of protection against breakthrough infections and hospitalizations in line with published evidence of its durable antibody and cellular immune response, although its Vaccine Effectiveness (VE) at baseline after a single-dose is lower than that for the two-dose mRNA vaccines. Additional studies are needed to understand durability following homologous or heterologous boosters.
Abstract: Background: Available SARS-CoV-2 vaccines have reduced efficacy against the Omicron variant in immunocompetent individuals. Kidney transplant recipients (KTRs) have diminished antiviral responses to wild-type SARS- CoV-2 after vaccination, and data on antiviral responses to SARS-CoV-2 variants, including the Omicron variant, are limited. Methods: We conducted a prospective, multi-center cohort study of 51 adult KTRs who received three doses of BNT162b2 or mRNA-1273. Blood and urine samples were collected before and four weeks after the third vaccine dose. The primary outcome was anti-viral antibody responses against wild-type and variants of SARS-CoV-2. Secondary objectives included occurrence of breakthrough SARS-CoV-2 infection and non-invasive monitoring for rejection using serum creatinine, proteinuria, donor-derived cell-free DNA and donor-specific antibodies. Sera from pre-pandemic healthy controls and KTRs were used for comparison. Results: 67% of KTRs developed anti-wild-type spike antibodies after the third vaccine dose, similar to the Alpha (51%) and Beta (53%) variants, but higher than the Gamma (39%) and Delta (25%) variants. No KTRs had neutralizing responses to the Omicron variant before the third vaccine dose. After the third dose, fewer KTRs had neutralizing responses to the Omicron variant (12%) compared to wild-type (61%) and Delta (59%) variants. Three patients (6%) developed breakthrough SARS-CoV-2 infection at a median of 89 days. No KTRs developed allograft injury, de novo donor-specific antibodies or allograft rejection. Conclusion: In KTRs, a third dose of mRNA vaccines increases antibody responses against wild-type and variants of SARS-CoV-2, while neutralizing responses to the Omicron variant remain markedly reduced.
Phase III Study of Novaferon in Non-hospitalized Adult Patients With Mild COVID-19 - Condition: Covid19
Interventions: Biological: Novaferon; Biological: Placebo
Sponsors: Genova Inc.; Tokyo Shinagawa Hospital
Recruiting
Human COVID-19 Immunoglobulin (COVID-HIG) Therapy for COVID-19 Patients - Condition: COVID-19
Interventions: Biological: Human COVID-19 immunoglobulin (pH4) for intravenous injection; Drug: Placebo
Sponsors: Sinopharm Wuhan Plasma-derived Biotherapies Co., Ltd.; China National Biotec Group Company Limited; Beijing Tiantan Biological Products Co., Ltd.
Not yet recruiting
A Telemedicine Brief Mindfulness Intervention in Post-COVID-19 - Condition: Post COVID-19
Intervention: Other: Mindfulness
Sponsors:
Fondazione Don Carlo Gnocchi Onlus; Catholic University of the Sacred Heart
Recruiting
Immunogenicity and Safety of a Booster Dose of the SpikoGen COVID-19 Vaccine - Condition: COVID-19
Interventions: Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant; Biological: Saline placebo
Sponsors: Cinnagen; Vaxine Pty Ltd
Active, not recruiting
A Safety, Tolerability, and Efficacy Study of IBI314 in Mild to Moderate Patients With COVID-19 - Condition: COVID-19
Interventions: Biological: IBI314(low dose); Biological: IBI314(high dose); Biological: IBI314(medium dose); Other: Placebo
Sponsor:
Innovent Biologics (Suzhou) Co. Ltd.
Not yet recruiting
PTX-COVID19-B, an mRNA Humoral Vaccine, Intended for Prevention of COVID-19 in a General Population. This Study is Designed to Demonstrate the Safety, Tolerability, and Immunogenicity of PTX-COVID19-B in Comparison to the Pfizer- BioNTech COVID-19 Vaccine. - Condition: Covid19 Vaccine
Interventions: Biological: PTX-COVID19-B; Biological: Pfizer- BioNTech COVID-19 vaccine; Biological: Placebo
Sponsor: Providence Therapeutics Holdings Inc.
Recruiting
Quality of Life and Lung Function on Post Covid-19 Patient - Condition: COVID-19
Intervention: Other: breathing exercise, Aerobic exercises
Sponsor: Qassim University
Recruiting
Multicenter Double Blind, Parallel-group Phase 2/3 Trial, to Study Raloxifene in Adult COVID-19 Patients. - Condition: SARS CoV 2 Infection
Interventions: Drug: Raloxifene; Other: Placebo
Sponsor: Dompé Farmaceutici S.p.A
Completed
Safety & Immunogenicity of Booster SARS-CoV-2 Vaccine (Vero Cell) - Condition: COVID-19
Intervention: Biological: SARS-COV-2 Vaccine (Vero Cell-Sinopharm) Inactivated
Sponsor: PT. Kimia Farma (Persero) Tbk
Not yet recruiting
Spa Rehabilitation, Antioxidant and Bioenergetic Supportive Treatment of Patients With Post-Covid-19 Syndrome - Condition: COVID-19 Respiratory Infection
Interventions: Dietary Supplement: ubiquinol (reduced coenzyme Q10); Other: mountain spa rehabilitation; Diagnostic Test: 2x14 ml of peripheral blood collected in a tube with anticoagulant
Sponsors: Comenius University; Sanatórium of Dr. Guhr, n.o.
Completed
Study to Evaluate the Effect of Nicotinamide Mononucleotide (NMN) As an Adjuvant to Standard of Care (SOC) On Fatigue Associated With COVID-19 Infection - Condition: COVID-19 Infection
Interventions: Other: Nicotinamide Mononucleotide; Other: Nicotinamide Mononucleotide with L-Leucine; Other: Placebo
Sponsor:
Vedic Lifesciences Pvt. Ltd.
Recruiting
A Live Recombinant Newcastle Disease Virus-vectored COVID-19 Vaccine Phase 1 Study. - Condition: SARS-CoV-2
Interventions: Drug: Sodium Chloride; Biological: NDV- HXP-S IN low dose; Biological: NDV-HXP-S IM low dose; Biological: NDV-HXP-S IN high dose; Biological: NDV- HXP-S IM high dose
Sponsor: Sean Liu
Recruiting
The Effectiveness of RPSG Intervention for Nurses During the COVID-19 - Condition: COVID-19 Acute Respiratory Distress Syndrome
Interventions: Behavioral: RPSG; Behavioral: AVMBM
Sponsor: National Taiwan University Hospital
Not yet recruiting
Symptom-based Rehabilitation Compared to Usual Care in Post-COVID - a Randomized Controlled Trial - Conditions: COVID-19; Long-COVID
Interventions: Other: symptom-focused rehabilitation; Other: usual care
Sponsors: Schön Klinik Berchtesgadener Land; Bavarian State Office for Health and Food Safety; Praxis im Zentrum Erlangen; Pneumologen Lichterfelde Berlin; Pneumopraxis Marburg; COVID ambulance Philipps-University Marburg; Pneumologie Elisenhof Munich; COVID ambulance Pneumology LMU Munich; COVID ambulance psychology LMU Munich; University Clinic Augsburg; COVID ambulance Schön Klinik Schönau
Not yet recruiting
Efficacy of Oral Rinses for Inactivation of COVID-19 (MOR2) - Conditions: COVID-19; Coronavirus Infection; SARS CoV 2 Infection
Interventions:
Other: Placebo Comparator: Sterile Water; Other: 27% Ethanol plus essential oils; Other: 0.075% Cetylpyridinium Chloride
Sponsor: University of North Carolina, Chapel Hill
Not yet recruiting
An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment - The COVID-19 pandemic is one of the greatest threats to human health in the 21st century with more than 257 million cases and over 5.17 million deaths reported worldwide (as of November 23, 2021. Various agents were initially proclaimed to be effective against SARS-CoV-2, the etiological agent of COVID-19. Hydroxychloroquine, lopinavir/ritonavir, and ribavirin are all examples of therapeutic agents, whose efficacy against COVID-19 was later disproved. Meanwhile, concentrated efforts of…
Antiviral activity of 5-aminolevulinic acid against variants of severe acute respiratory syndrome coronavirus 2 - CONCLUSION: Our study suggests that 5-ALA with SFC warrants accelerated clinical evaluation as an antiviral drug candidate for treating patients infected with SARS-CoV-2 variants.
Nafamostat reduces systemic inflammation in TLR7-mediated virus-like illness - CONCLUSIONS: Our data indicate that R848 administration provides a useful model of ssRNA virus infection, which induces inflammation in the periphery and CNS, and virus infection-like illness. In turn, we show that nafamostat has a systemic anti-inflammatory effect in the presence of the TLR7/8 agonist. Therefore, the results indicate that nafamostat has anti-inflammatory actions, beyond its ability to inhibit TMPRSS2, that might potentiate its anti-viral actions in pathologies such as COVID-19.
Inflammasome activation in neutrophils of patients with severe COVID-19 - Infection by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) engages the inflammasome in monocytes and macrophages and leads to the cytokine storm in COVID-19. Neutrophils, the most abundant leukocytes, release neutrophil extracellular traps (NETs), which have been implicated in the pathogenesis of COVID-19. Our recent study shows that activation of the NLRP3 inflammasome is important for NET release in sterile inflammation. However, the role of neutrophil inflammasome formation…
Cangma Huadu granules, a new drug with great potential to treat coronavirus and influenza infections, exert its efficacy through anti-inflammatory and immune regulation - CONCLUSION: CMHD can significantly combats viral infections caused by HCoV-229E and H1N1, and the mechanism may be related to its multiple functions of anti-inflammatory, immunity regulating and inhibiting NF-κB signal transduction pathway.
Interferon Control of Human Coronavirus Infection and Viral Evasion: Mechanistic Insights and Implications for Antiviral Drug and Vaccine Development - Recognition of viral infections by various pattern recognition receptors (PRRs) activates an inflammatory cytokine response that inhibits viral replication and orchestrates the activation of adaptive immune responses to control the viral infection. The broadly active innate immune response puts a strong selective pressure on viruses and drives the selection of variants with increased capabilities to subvert the induction and function of antiviral cytokines. This revolutionary process dynamically…
Sandacrabins - Structurally unique antiviral RNA polymerase inhibitors from a rare myxobacterium - We report structure elucidation and total synthesis of five unprecedented terpenoid-alkaloids, the sandacrabins, alongside with the first description of their producing organism Sandaracinus defensii MSr10575, which expands the Sandaracineae family by only its second member. The genome sequence of S. defensii as presented in this study was utilized to identify enzymes responsible for sandacrabin formation, whereby dimethylbenzimidazol, deriving from cobalamin biosynthesis, was identified as key…
A novel antagonist of TRPM2 and TRPV4 channels: Carvacrol - The overload cytosolic free Ca^(2+) (cCa^(2+)) influx-mediated excessive generation of oxidative stress in the pathophysiological conditions induces neuronal and cellular injury via the activation of cation channels. TRPM2 and TRPV4 channels are activated by oxidative stress, and their specific antagonists have not been discovered yet. The antioxidant and anti-Covid-19 properties of carvacrol (CARV) were recently reported. Hence, I suspected possible antagonist properties of CARV against…
A New Remote Guided Method for Supervised Web-Based Cognitive Testing to Ensure High-Quality Data: Development and Usability Study - CONCLUSIONS: These data suggest that the RGT methodology could help ameliorate concerns regarding online data quality- particularly for studies involving high-risk or rare cohorts-and offer an alternative for collecting high-quality human cognitive data without requiring in-person physical attendance.
Obatoclax inhibits SARS-CoV-2 entry by altered endosomal acidification and impaired cathepsin and furin activity in vitro - Coronavirus disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has set off a global pandemic. There is an urgent unmet need for safe, affordable, and effective therapeutics against COVID-19. In this regard, drug repurposing is considered as a promising approach. We assessed the compounds that affect the endosomal acidic environment by applying human angiotensin-converting enzyme 2 (hACE2)-expressing cells infected with a SARS-CoV-2 spike…
Antiviral drugs : Potent agents, promising therapies for COVID-19 and therapeutic limitations - Antiviral drugs inhibit viral replication by interaction with specific elements of the viral replication cycle. Directly acting antiviral agents have revolutionized the therapeutic options for chronic infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). Pharmacological developments constantly improve therapeutic and prophylactic options for diseases caused by herpes viruses, which is of particular relevance for immunocompromised patients. While…
Structures and therapeutic potential of anti-RBD human monoclonal antibodies against SARS-CoV-2 - Background: Administration of potent anti-receptor-binding domain (RBD) monoclonal antibodies has been shown to curtail viral shedding and reduce hospitalization in patients with SARS-CoV-2 infection. However, the structure-function analysis of potent human anti-RBD monoclonal antibodies and its links to the formulation of antibody cocktails remains largely elusive. Methods: Previously, we isolated a panel of neutralizing anti-RBD monoclonal antibodies from convalescent patients and showed their…
Case Report: Clinical Management of a Patient With Metastatic Non-Small Cell Lung Cancer Newly Receiving Immune Checkpoint Inhibition During Symptomatic COVID-19 - Effects of initiation of programmed-death-protein 1 (PD1) blockade during active SARS-CoV-2 infection on antiviral immunity, COVID-19 course, and underlying malignancy are unclear. We report on the management of a male in his early 40s presenting with highly symptomatic metastatic lung cancer and active COVID-19 pneumonia. After treatment initiation with pembrolizumab, carboplatin, and pemetrexed, the respiratory situation initially worsened and high-dose corticosteroids were initiated due to…
Activation of Sphingomyelinase-Ceramide-Pathway in COVID-19 Purposes Its Inhibition for Therapeutic Strategies - Effective treatment strategies for severe coronavirus disease (COVID-19) remain scarce. Hydrolysis of membrane-embedded, inert sphingomyelin by stress responsive sphingomyelinases is a hallmark of adaptive responses and cellular repair. As demonstrated in experimental and observational clinical studies, the transient and stress-triggered release of a sphingomyelinase, SMPD1, into circulation and subsequent ceramide generation provides a promising target for FDA- approved drugs. Here, we report…
Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach - The four Janus kinase (JAK) proteins and seven signal transducer and activator of transcription (STAT) transcription factors mediate intracellular signal transduction downstream of cytokine receptors, which are implicated in the pathology of autoimmune, allergic and inflammatory diseases. Development of targeted small-molecule therapies such as JAK inhibitors, which have varied selective inhibitory profiles, has enabled a paradigm shift in the treatment of diverse disorders. JAK inhibitors…
Hung Thanh Phan COVID-19 NEW SOLUTION - - link
METHODS OF TREATING SARS-COV-2 INFECTION - - link
피라졸 유도체의 폐섬유증 치료제 - 본 발명은 피라졸 유도체인 하기 화학식 1의 화합물 또는 이의 약학적으로 허용가능한 염을 포함하는, 폐섬유증 치료용 약학적 조성물 또는 항바이러스제를 제공한다 <화학식 1>
(상기 화학식 1에서 R은 발명의 설명에서 정의한 바와 같다.).
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66 - [link](https://patentscope.wipo.int/search/en/detail.jsf?docId=KR345008871)一种疾病相关标志物的筛选方法、应用及试剂盒 - 本发明公开了一种疾病相关标志物的筛选方法、应用及试剂盒。筛选方法包括：使用能够结合免疫球蛋白（Ig）的物质，分别从第一批健康样本血清和患病样本血清中纯化出Ig复合物；将与Ig相结合的蛋白进行蛋白质谱测序分析，比较健康样本与患病样本的差异，找到只出现在患病样本中的差异蛋白，即为该疾病相关潜在标志物。另外还可以通过以下步骤进一步验证该潜在标志物：使用第二批健康样本和患病样本的血清（扩大病例），纯化获得Ig复合物，利用差异蛋白的特异性抗体进行进一步鉴定。该方法先从血清中获得Ig复合物（而不是全血清），再将与Ig相结合的蛋白进行蛋白质谱测序联合特异性抗体分析，能够快速有效地筛选出疾病相关标志物。 - link
一种慢性淋巴细胞白血病SSCR风险模型及其建立方法和应用 - 本发明提供一种慢性淋巴细胞白血病SSCR风险模型及其建立方法和应用，属于疾病预后和分子生物学技术领域。本发明采用高通量测序的慢性淋巴细胞白血病(CLL)表达谱，进一步证实CLL的异质性，验证基于CLL细胞分化的CLL患者分类，预测患者预后。本发明将CLL细胞按分化状态分为两组，并对CLL细胞分化相关基因进行鉴定。最后，选择4个最具预后意义的CLL细胞分化相关基因，建立基于CLL细胞分化相关基因的SSCR风险评分模型，经验证该风险评分模型对CLL患者总生存期及首次治疗时间预测具有良好的可靠性。该评分系统可以帮助医生根据CLL细胞分化状况预测患者的预后，选择最佳的治疗方案，具有良好的实际应用价值。 - link
一种流感新冠联合疫苗及其制备方法 - 本发明公开了一种流感新冠联合疫苗，包括以下质量浓度的原料：含RBD‑Fc融合蛋白的重组新冠疫苗1‑100μg/mL；含H1N1型流感病毒的流感亚单位疫苗1‑50μg/mL；含H3N2型流感病毒的流感亚单位疫苗1‑50μg/mL；含B型流感病毒的流感亚单位疫苗1‑50μg/mL；氢氧化铝溶液，其中铝离子在流感新冠联合疫苗中的终浓度为0.5‑2.0mg/mL；余量为PBS磷酸缓冲液。制备方法：称取各原料；将四种疫苗分别用PBS磷酸缓冲液稀释后与氢氧化铝溶液混合；按照等体积比例混合，即得。本发明为含铝佐剂的新型冠状病毒疫苗和含铝佐剂的流感亚单位疫苗的联合疫苗，联合后，两种抗原组分疫苗之间没有相互抑制，能很好兼容。 - link
REAL-TIME REST BREAK MANAGEMENT SYSTEM FOR WORKPLACE - The present invention relates to a real-time rest break management system for workplace that comprises of a work desk, wherein first portion is incorporated with a biometric unit 4 for authenticating first user, and a second portion with a telescopic panel 2 associated with a weight sensor 6 and timer unit 7 calculating weight of head/hand manifesting user presence and their resting time period is mounted with an inflated cushion 5, an interactive primary display unit 1 attached over desk enables user to set first/second threshold time for sleeping/taking break, further linked with a tracking interface keeping track of activities and a vibrating unit crafted inside the cushion 5 which is linked to a secondary display unit 8 of second user, giving them access to actuate vibrating unit generating impulses to wake first user when threshold time period is exceeded by the first user. - link
一种瑞德西韦的合成方法 - 本发明涉及一种瑞德西韦的合成方法，包括以下步骤：将(2R,3R,4S,5R)‑2‑(4‑氨基吡咯[2,1‑f][1,2,4]三嗪‑7‑基)‑3,4‑二羟基‑5‑(羟甲基)四氢呋喃‑2‑碳腈、2,2‑二甲氧基丙烷和第一酸催化剂加入第一溶剂中，搅拌，经2,2‑二甲氧基丙烷保护邻二羟基合成中间体4，反应完毕后调碱降温；将无水氯化镁和中间体7加入反应中，通氮气流保护，搅拌均匀后滴加碱催化剂，升温搅拌，合成中间体5，反应完毕后进行提取分液；向反应中滴加第二酸催化剂，搅拌，经过后处理得到瑞德西韦粗品。本发明的三步反应均以第一溶剂为介质进行反应，仅在三步反应完成后进行后处理浓缩溶剂，减少浓缩溶剂的次数，降低工业成本。 - link
一种基于宏基因组学的病原微生物检测方法及装置 - 本发明公开了一种基于宏基因组学的病原微生物检测方法及装置，包括：获取待检测样本的宏基因组测序数据；对宏基因组测序数据进行预处理，得到目标数据；对目标数据进行筛选，得到目标序列；对目标序列进行聚类分析，获得待测样本的候选物种类别；将目标数据与非冗余参考基因集进行比对，并计算每个基因在单个样本中的丰度，得到待测样本的目标物种分类信息；将目标数据与病原微生物可检测数据库中的信息进行比对，获得待测样本的耐药基因和毒性元件信息；将目标物种分类信息、耐药基因和毒性元件信息，确定为待检测样本的检测结果。本发明提升了病原微生物检测适用性范围和病原检测准确性。 - link
CONJUNTO DE ESCOBILLA Y ESCOBILLERO CON AUTOLIMPIEZA - - link