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2.
arxiv; 2024.
Preprint Dans Anglais | PREPRINT-ARXIV | ID: ppzbmed-2401.18047v1

Résumé

Epidemiological models are best suitable to model an epidemic if the spread pattern is stationary. To deal with non-stationary patterns and multiple waves of an epidemic, we develop a hybrid model encompassing epidemic modeling, particle swarm optimization, and deep learning. The model mainly caters to three objectives for better prediction: 1. Periodic estimation of the model parameters. 2. Incorporating impact of all the aspects using data fitting and parameter optimization 3. Deep learning based prediction of the model parameters. In our model, we use a system of ordinary differential equations (ODEs) for Susceptible-Infected-Recovered-Dead (SIRD) epidemic modeling, Particle Swarm Optimization (PSO) for model parameter optimization, and stacked-LSTM for forecasting the model parameters. Initial or one time estimation of model parameters is not able to model multiple waves of an epidemic. So, we estimate the model parameters periodically (weekly). We use PSO to identify the optimum values of the model parameters. We next train the stacked-LSTM on the optimized parameters, and perform forecasting of the model parameters for upcoming four weeks. Further, we fed the LSTM forecasted parameters into the SIRD model to forecast the number of COVID-19 cases. We evaluate the model for highly affected three countries namely; the USA, India, and the UK. The proposed hybrid model is able to deal with multiple waves, and has outperformed existing methods on all the three datasets.


Sujets)
COVID-19 , Incapacités d'apprentissage , Mort cérébrale
3.
preprints.org; 2023.
Preprint Dans Anglais | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202312.0842.v1

Résumé

Antimicrobial resistance (AMR) is a growing public health issue worldwide that affects the world economy. The concern associated with this issue increased during the COVID-19 pandemic. The misuse of antibiotics during the COVID-19 pandemic will have catastrophic implications for the control of AMR. In 2019, the coronavirus illness COVID-19 first appeared in China. COVID-19 infection is a surface-to-surface communicable disease. It is considered the most vital global health disaster of the century. It has rapidly spread around the world and is the greatest challenge for humankind. This chapter discusses the origin, symptoms, transmission, treatment, and recommendations of the COVID-19 disease.


Sujets)
COVID-19
4.
medrxiv; 2023.
Preprint Dans Anglais | medRxiv | ID: ppzbmed-10.1101.2023.08.25.23294654

Résumé

Background: Post-coronavirus disease (COVID) is widely reported but the data of Post COVID-19 after infection with the Omicron variant is limited. This prospective study was conducted to determine the prevalence, pattern, and duration of symptoms related to Covid-19 recovered patients. Methods: Adults (>18 years old) in 11 districts of Delhi who had recovered from Covid-19 were followed up at 3 months and 6 months post-recovery. Results: The study found that the participants had a mean age of 42.07 years, with a standard deviation of 14.89. Additionally, a significant proportion of the participants (79.7%) experienced post-Covid symptoms. The participants elicited a history of Joint Pain (36%), Persistent dry cough (35.7%), anxiousness (28.4%) and shortness of breath (27.1%). The other symptoms reported were persistent fatigue (21.6%), persistent headache (20%), forgetfulness (19.7%) and weakness in limbs (18.6%). The longest duration of symptom was observed in participants reporting anxiousness (138.75 +54.14) followed by fatigue (137.57+48.33), shortness of breath (131.89+60.21) and joint pain/swelling (131.59+58.76). During the first follow-up, 2.2% of participants had an abnormal ECG reading, while no abnormalities were reported during the second follow-up. Additionally, 4.06% of participants had abnormal chest X-ray findings during the first follow-up, with this number decreasing to 2.16% during the second follow-up. Conclusion: Our study concluded that the clinical symptoms persist in participants until 6 months and a multi-system involvement is seen in the post-COVID period. Thus, the findings necessitate long-term, regular follow-ups.


Sujets)
Infections à coronavirus , Douleur , Céphalée , Dyspnée , Toux , Faiblesse musculaire , Arthralgie , COVID-19 , Fatigue
5.
medrxiv; 2023.
Preprint Dans Anglais | medRxiv | ID: ppzbmed-10.1101.2023.07.12.23292570

Résumé

BackgroundWastewater monitoring is increasingly used for community surveillance of infectious diseases, especially after the COVID-19 pandemic as the genomic footprints of pathogens shed by infected individuals can be traced in the environment. However, detection and concentration of pathogens in the environmental samples and their efficacy in predicting infectious diseases can be influenced by meteorological conditions and quality of samples. ObjectivesThis research examines whether meteorological conditions and sample pH affect SARS-CoV-2 concentrations in wastewater samples, and whether the association of SARS-CoV-2 with COVID-19 cases and mortality improves when adjusted for meteorological conditions and sample pH value in Miami-Dade County, FL. MethodsDaily wastewater samples were collected from Miami-Dade Wastewater Treatment Plant in Key Biscayne, Florida from August 2021 to August 2022. The samples were analyzed for pH and spiked with OC43. RNA was extracted from the concentrated wastewater sample and SARS-CoV-2 was quantified using qPCR. COVID-19 and mortality data were acquired from the Centers for Disease Control and Prevention (CDC) and meteorological data from the National Climatic Data Center. COVID-19 case and mortality rates were modelled with respect to time-lagged wastewater SARS-CoV-2 adjusting for meteorological conditions, and sample pH value and OC43 recovery. ResultsTemperature, dew point, pH values and OC43 recovery showed significant associations with wastewater SARS-CoV-2. Time-lagged wastewater SARS-CoV-2 showed significant associations with COVID-19 case and mortality incidence rates. This association improved when wastewater SARS-CoV-2 levels were adjusted for (or instrumented on) meteorological conditions, OC43 recovery, and sample pH. A 0.47% change in COVID-19 case incidence rate was associated with 1% change in wastewater SARS-CoV-2 ({beta} [~] 0.47; 95% CI = 0.29 - 0.64; p < 0.001). A 0.12 % change in COVID-19 mortality rate was associated with 1 % change in SARS-CoV-2 in wastewater 44 days prior. A 0.07% decline in COVID-19 mortality rate was associated with a unit increase in ambient temperature 28 days prior. DiscussionTime lagged wastewater SARS-CoV-2 (and its adjustment for sample pH and RNA recovery) and meteorological conditions can be used for the surveillance of COVID-19 case and mortality. These findings can be extrapolated to improve the surveillance of other infectious diseases by proactive measurements of infectious agent(s) in the wastewater samples, adjusting for meteorological conditions and sample pH value.


Sujets)
COVID-19 , Maladies transmissibles
6.
BMJ Case Rep ; 16(4)2023 Apr 26.
Article Dans Anglais | MEDLINE | ID: covidwho-2304125

Résumé

A man in his early 20s presented with acute loss of vision in his only eye, the left eye (OS), and was on oral steroids. He had lost vision in his right eye during his childhood and the cause was unknown. There was no history of trauma. Best-corrected visual acuity (BCVA) in OS was 20/100 and in the right eye was hand movements. OS showed non-granulomatous keratic precipitates on the cornea, anterior chamber flare 1+ and cell 1+, early cataract, vitreous haze and cells 2+ with nasal retinal detachment and superior full thickness retinitis. He underwent pars plana vitrectomy with intravitreal ganciclovir and barrage laser away from the necrotic retina. PCR for herpes simplex virus 2 was positive from the aqueous and vitreous sample. He was started on oral valacyclovir 1 g three times a day and continued on tapering dose of oral steroids. BCVA in OS at 6-month follow-up was 20/25.


Sujets)
Décollement de la rétine , Syndrome de nécrose rétinienne aigüe , Mâle , Humains , Enfant , Herpèsvirus humain de type 2 , Études de suivi , Décollement de la rétine/étiologie , Décollement de la rétine/chirurgie , Rétine , Vitrectomie
7.
Ocul Immunol Inflamm ; : 1-4, 2022 Feb 03.
Article Dans Anglais | MEDLINE | ID: covidwho-2285415

Résumé

AIM: To report a case of unilateral acute idiopathic maculopathy (UAIM) following SARS-CoV-2 virus infection. CASE DESCRIPTION: A 44-year-old male patient, infected with SARS-CoV-2 virus previously, presented to the retina department with complaints of sudden blurring of vision in right eye. His presenting visual acuity in right eye was 20/30, N8. Fundus showed an irregular area of yellowish-white subretinal lesion at the macula involving the fovea with reddish-brown pigment clumps. Retinal imaging findings were consistent with the diagnosis of UAIM. No treatment was given. RESULTS: The imaging findings showed improvement at day 7 post-presentation with improvement in vision to 20/20, N6. At final visit (5-week post presentation), visual acuity was maintained at 20/20, N6 and there was no recurrence of findings. EXPERT OPINION: Unilateral acute idiopathic maculopathy might be associated with SARS-CoV-2 virus infection. CONCLUSION: Infection with SARS-CoV-2 virus might be associated with UAIM. Such an association has not yet been described in the literature.

8.
researchsquare; 2023.
Preprint Dans Anglais | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2799947.v1

Résumé

Objective: COVID-19-associated pulmonary aspergillosis (CAPA) remains a high mortality mycotic infection throughout the pandemic, and glucocorticoids (GCs) may be its root cause. We aimed to evaluate the effect of systemic GC treatment on the development of CAPA. Methods: We systematically searched the PubMed, Google Scholar, Scopus, and Embase databases to collect eligible studies published until December 31, 2022. The pooled outcome of CAPA development was calculated as the log odds ratio (LOR) with 95% confidence intervals (CI) using a random effect model. Results: A total of 21 studies with 5174 patients were included. Of these, 20 studies with 4675 patients consisting of 2565 treated with GC but without other immunomodulators (GC group) and 2110 treated without GC and other immunomodulators (controls) were analyzed. The pooled LOR of CAPA development was higher for the GC group than for the control group (0.54; 95% CI: 0.22, 0.86; p<0.01). In the subgroups, the pooled LOR was higher for high-dose GC (0.90; 95% CI: 0.17, 1.62: p=0.01) and dexamethasone (0.71; 95% CI: 0.35, 1.07; p<0.01)-treated patients, but there was no significant difference for low-dose GC (0.41; 95% CI: -0.07, 0.89; p=0.09)- and non-dexamethasone GC (0.21; 95% CI: -0.36, 0.79; p=0.47)-treated patients versus controls. Conclusion: GC treatment increased the risk of CAPA development, and the risk was associated with the use of high-dose GC or dexamethasone therapy.


Sujets)
COVID-19 , Aspergillose pulmonaire , Mycoses oculaires
10.
Proc Assoc Inf Sci Technol ; 59(1): 570-574, 2022.
Article Dans Anglais | MEDLINE | ID: covidwho-2085191

Résumé

The fight against the COVID-19 pandemic is as much an information war as it is a medical war. Members from South Asia and the Asia Pacific countries share their experiences and challenges faced with collaborative responses for the ASIS&T Special Chapter funded project on "Dealing with COVID-19 and saving people's lives in South Asia (SA) areas & beyond-A Health Informatics Promotion Project" awarded to the South Asia Chapter in 2021. The panel discusses the challenges faced within the context of geopolitical, socio-economic, religious, and cultural conditions prevalent within their countries. In the first 40 minutes, panel members narrate their own experiences by sharing their personal stories about this collaborative project and share the challenges of content creation and promotion from within the context of their respective countries. The next 30 minutes will be facilitated by the panel chair inviting a discussion between panel members and the audience to engage and come up with innovative ideas, discuss challenges in creating multilingual content and suggestions for improving the project outcome as well as shed light on initiating future health informatics project in similar regions. The last 20 minutes will culminate with the summarization of these collaborative experiences.

11.
J Diabetes Complications ; 36(9): 108284, 2022 09.
Article Dans Anglais | MEDLINE | ID: covidwho-1983396

Résumé

BACKGROUND: There was an unprecedented increase in COVID-19-associated-Mucormycosis (CAM) cases during the second pandemic wave in India. METHODS: This observational study was done to know the epidemiological profile of CAM cases andincluded all patients admitted with mucormycosis between May 2021 and July 2021. RESULTS: Out of the enrolled 208 CAM cases (either SARS-CoV-2 RT-PCR or serology positive), 204, three and one had rhino-orbital-cerebral, pulmonary and gastrointestinal mucormycosis, respectively. 95.7 % of the patients had diabetes, out of which 42.3 % were recently diagnosed. Mean HbA1c was 10.16 ± 2.56 %. 82.5 % of the patients were unvaccinated. During their COVID-19 illness, 86.5 % were prescribed antibiotics, 84.6 % zinc preparations, 76.4 % ivermectin, and 64.9 % steroids, while only 39.5 % required oxygen therapy. The frequency of blood groups A, B, O and AB in our CAM patients was 29.5 %, 18.9 %, 38.9 % &12.6 %, respectively. At three months follow up, 60 (28.8 %) patients died, four (1.9 %) stopped antifungal treatment, and 144(69.23 %) were on antifungal treatment. 55 % (n = 33) of deaths occurred within 15 days of admission. Mortality was significantly associated with higher age, RT-PCR positive for SARS-CoV-2, raised serum creatinine and alkaline phosphatase during treatment. At 6 months follow-up, eight more patients died, three due to chronic kidney disease, four patients who had stopped treatment and one patient who was on a ventilator due to COVID-19 associated pneumonia and the rest 140(67.3 %) survived. CONCLUSION: Uncontrolled hyperglycemia, SARS-CoV-2 infection, rampant use of antibiotics, zinc supplementation and steroids were some of the risk factors for mucormycosis. Despite the overwhelming number of patients with an uncommon disease like mucormycosis, the six months mortality was much lower than expected.


Sujets)
COVID-19 , Mucormycose , Antibactériens , Antifongiques/usage thérapeutique , COVID-19/complications , COVID-19/épidémiologie , Études épidémiologiques , Humains , Mucormycose/complications , Mucormycose/diagnostic , Mucormycose/épidémiologie , SARS-CoV-2 , Zinc
12.
Mycoses ; 65(11): 1010-1023, 2022 Nov.
Article Dans Anglais | MEDLINE | ID: covidwho-1896014

Résumé

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been widely reported but homogenous large cohort studies are needed to gain real-world insights about the disease. METHODS: We collected clinical and laboratory data of 1161 patients hospitalised at our Institute from March 2020 to August 2021, defined their CAPA pathology, and analysed the data of CAPA/non-CAPA and deceased/survived CAPA patients using univariable and multivariable models. RESULTS: The overall prevalence and mortality of CAPA in our homogenous cohort of 1161 patients were 6.4% and 47.3%, respectively. The mortality of CAPA was higher than that of non-CAPA patients (hazard ratio: 1.8 [95% confidence interval: 1.1-2.8]). Diabetes (odds ratio [OR] 1.92 [1.15-3.21]); persistent fever (2.54 [1.17-5.53]); hemoptysis (7.91 [4.45-14.06]); and lung lesions of cavitation (8.78 [2.27-34.03]), consolidation (9.06 [2.03-40.39]), and nodules (8.26 [2.39-28.58]) were associated with development of CAPA by multivariable analysis. Acute respiratory distress syndrome (ARDS) (2.68 [1.09-6.55]), a high computed tomography score index (OR 1.18 [1.08-1.29]; p < .001), and pulse glucocorticoid treatment (HR 4.0 [1.3-9.2]) were associated with mortality of the disease. Whereas neutrophilic leukocytosis (development: 1.09 [1.03-1.15] and mortality: 1.17 [1.08-1.28]) and lymphopenia (development: 0.68 [0.51-0.91] and mortality: 0.40 [0.20-0.83]) were associated with the development as well as mortality of CAPA. CONCLUSION: We observed a low but likely underestimated prevalence of CAPA in our study. CAPA is a disease with high mortality and diabetes is a significant factor for its development while ARDS and pulse glucocorticoid treatment are significant factors for its mortality. Cellular immune dysregulation may have a central role in CAPA from its development to mortality.


Sujets)
COVID-19 , Aspergillose pulmonaire , , COVID-19/complications , COVID-19/épidémiologie , Études de cohortes , Soins de réanimation , Glucocorticoïdes , Humains , Aspergillose pulmonaire/complications , Aspergillose pulmonaire/épidémiologie
13.
Exp Biol Med (Maywood) ; 247(14): 1244-1252, 2022 07.
Article Dans Anglais | MEDLINE | ID: covidwho-1846736

Résumé

The spread of SARS-CoV-2 over the entire world is more commonly known as COVID-19. COVID-19 has impacted society in every aspect of routine life. SARS-CoV-2 infection is often misdiagnosed as influenza or seasonal upper respiratory tract viral infections. General diagnostic tools can detect the viral antigen or isotypes of antibodies. However, inter- and intraindividual variations in antibody levels can cause false negatives in antibody immunoassays. On the contrary, the false-positive test results can also occur due to either cross-reactivity of the viral antigens or some other patient-related autoimmune factors. There is need for a cogent diagnostic tool with more specificity, selectivity, and reliability. Here, we have described the potential of convalescent serum-derived exosome as a diagnostic tool for the detection of SARS-CoV-2, even in asymptomatic patients, which is a limitation for currently practiced diagnostic tests throughout the globe. In addition, its potential as a vehicle for messenger RNA (mRNA) delivery is also emphasized.


Sujets)
COVID-19 , Exosomes , Anticorps antiviraux , COVID-19/diagnostic , COVID-19/thérapie , Dépistage de la COVID-19 , Humains , Immunisation passive , ARN messager/génétique , Reproductibilité des résultats , SARS-CoV-2 ,
14.
ssrn; 2022.
Preprint Dans Anglais | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.4091699

Sujets)
COVID-19
15.
Biomed Chromatogr ; 36(6): e5363, 2022 Jun.
Article Dans Anglais | MEDLINE | ID: covidwho-1748781

Résumé

Favipiravir finished dosage was approved for emergency use in many countries to treat SARS-CoV-2 patients. A specific, accurate, linear, robust, simple, and stability-indicating HPLC method was developed and validated for the determination of degradation impurities present in favipiravir film-coated tablets. The separation of all impurities was achieved from the stationary phase (Inert sustain AQ-C18, 250 × 4.6 mm, 5-µm particle) and mobile phase. Mobile phase A contained KH2 PO4 buffer (pH 2.5 ± 0.05) and acetonitrile in the ratio of 98:2 (v/v), and mobile phase B contained water and acetonitrile in the ratio of 50:50 (v/v). The chromatographic conditions were optimized as follows: flow rate, 0.7 mL/min; UV detection, 210 nm; injection volume, 20 µL; and column temperature, 33°C. The proposed method was validated per the current International Conference on Harmonization Q2 (R1) guidelines. The recovery study and linearity ranges were established from the limit of quantification to 150% optimal concentrations. The method validation results were found to be between 98.6 and 106.2% for recovery and r2  = 0.9995-0.9999 for linearity of all identified impurities. The method precision results were achieved below 5% of relative standard deviation. Forced degradation studies were performed in chemical and physical stress conditions. The compound was sensitive to chemical stress conditions. During the study, the analyte degraded and converted to unknown degradation impurities, and its molecular mass was found using the LC-MS technique and established degradation pathways supported by reaction of mechanism. The developed method was found to be suitable for routine analysis of research and development and quality control.


Sujets)
COVID-19 , SARS-CoV-2 , Acétonitriles , Amides , Chromatographie en phase liquide à haute performance/méthodes , Chromatographie en phase liquide/méthodes , Contamination de médicament , Stabilité de médicament , Humains , Pyrazines , Reproductibilité des résultats , Spectrométrie de masse en tandem/méthodes
16.
Mycoses ; 65(5): 567-576, 2022 May.
Article Dans Anglais | MEDLINE | ID: covidwho-1741479

Résumé

BACKGROUND: The sudden surge of mucormycosis cases which happened during the second wave of COVID-19 pandemic was a significant public health problem in India. OBJECTIVES: The aim of this study was to analyse the clinico-epidemicological characteristics of the mucormycosis cases to determine the changes that had occurred due to COVID-19 pandemic. METHODOLOGY: A retrospective cross-sectional study was conducted at the Department of Otolaryngology Head and Neck Surgery, PGIMER, Chandigarh, India. Patients diagnosed with rhino-orbital mucormycosis were categorised into the following groups: Pre-pandemic(May 2019 to April 2020), Pandemic Pre-epidemic (May 2020 to April 2021) and Epidemic (1 May 2021 to 12 July 2021). The epidemiological, clinical and surgical data of all the patients were retrieved from the hospital records and analysed. RESULTS: The epidemic period had 370 cases, compared with 65 during pandemic period and 42 in the pre-pandemic period. Diabetes mellitus was seen in 87% of cases during epidemic period, 92.9% in the pre-pandemic period and 90.8% in the pre-pandemic pre-epidemic period. The proportion of patients suffering from vision loss, restricted extra-ocular movements, palatal ulcer and nasal obstruction was higher in the pre-epidemic groups, and the difference was significant (p, <.01). There was no history of oxygen use in 85.9% of patients and no steroid use in 76.5%. The death rates were the lowest during epidemic (10%). CONCLUSION: COVID-19 has caused a statistically significant increase in the number of mucormycosis infections. The mortality and morbidity which showed an increase during the first wave of COVID-19 decreased significantly during the epidemic period.


Sujets)
COVID-19 , Mucormycose , COVID-19/épidémiologie , Études transversales , Champignons , Humains , Mucormycose/diagnostic , Pandémies , Études rétrospectives
17.
medrxiv; 2022.
Preprint Dans Anglais | medRxiv | ID: ppzbmed-10.1101.2022.03.14.22272314

Résumé

ABSTRACT Importance Genomic footprints of pathogens shed by infected individuals can be traced in environmental samples. Analysis of these samples can be employed for noninvasive surveillance of infectious diseases. Objective To evaluate the efficacy of environmental surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for predicting COVID-19 cases in a college dormitory. Design Using a prospective experimental design, air, surface swabs, and wastewater samples were collected from a college dormitory from March to May 2021. Students were randomly screened for COVID-19 during the study period. SARS-CoV-2 in environmental samples was concentrated with electronegative filtration and quantified using Volcano 2 nd Generation-qPCR. Descriptive analyses were conducted to examine the associations between time-lagged SARS-CoV-2 in environmental samples and clinically diagnosed COVID-19 cases. Setting This study was conducted in a residential dormitory at the University of Miami, Coral Gables campus, FL, USA. The dormitory housed about 500 students. Participants Students from the dormitory were randomly screened, for COVID-19 for 2-3 days / week while entering or exiting the dormitory. Main Outcome Clinically diagnosed COVID-19 cases were of our main interest. We hypothesized that SARS-CoV-2 detection in environmental samples was an indicator of the presence of local COVID-19 cases in the dormitory, and SARS-CoV-2 can be detected in the environmental samples several days prior to the clinical diagnosis of COVID-19 cases. Results SARS-CoV-2 genomic footprints were detected in air, surface swab and wastewater samples on 52 (63.4%), 40 (50.0%) and 57 (68.6%) days, respectively, during the study period. On 19 (24%) of 78 days SARS-CoV-2 was detected in all three sample types. Clinically diagnosed COVID-19 cases were reported on 11 days during the study period and SARS-CoV-2 was also detected two days before the case diagnosis on all 11 (100%), 9 (81.8%) and 8 (72.7%) days in air, surface swab and wastewater samples, respectively. Conclusion Proactive environmental surveillance of SARS-CoV-2 or other pathogens in a community/public setting has potential to guide targeted measures to contain and/or mitigate infectious disease outbreaks. Key Points Question How effective is environmental surveillance of SARS-CoV-2 in public places for early detection of COVID-19 cases in a community? Findings All clinically confirmed COVID-19 cases were predicted with the aid of 2 day lagged SARS-CoV-2 in environmental samples in a college dormitory. However, the prediction efficiency varied by sample type: best prediction by air samples, followed by wastewater and surface swab samples. SARS-CoV-2 was also detected in these samples even on days without any reported cases of COVID-19, suggesting underreporting of COVID-19 cases. Meaning SARS-CoV-2 can be detected in environmental samples several days prior to clinical reporting of COVID-19 cases. Thus, proactive environmental surveillance of microbiome in public places can serve as a mean for early detection of location-time specific outbreaks of infectious diseases. It can also be used for underreporting of infectious diseases.


Sujets)
COVID-19 , Infections à coronavirus , Maladies transmissibles
18.
researchsquare; 2022.
Preprint Dans Anglais | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1336801.v1

Résumé

TANK-binding kinase 1 (TBK1) is a key signalling component that drives the production of type-I interferons (IFNs), which have essential antiviral activities including against SARS-CoV-2. TBK1 and its homolog IκB kinase-ε (IKKε) can also induce the production of pro-inflammatory factors that contribute to pathogen clearance. While initially protective, delayed engagement of type-I IFN is associated with lethal hyper-inflammation seen in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to this response is unknown. We have discovered that the small molecule idronoxil inhibits both IRF3 and NF-κB-driven inflammation by disrupting the formation of TBK1/IKKε signalling complexes following STING activation. Leveraging this unique activity, we show that therapeutic administration of idronoxil suppresses cellular and molecular lung inflammation in K18-hACE2 mice challenged with SARS-CoV-2, resulting in reduced pro-inflammatory cytokine production and decreased airway fibrosis in experimental COVID-19. Our results indicate a critical role for TBK1/IKKε signalling in SARS-CoV-2 hyper-inflammation and identify a novel therapeutic intervention to limit disease severity in COVID-19 patients.


Sujets)
COVID-19
19.
Therapie ; 77(3): 319-328, 2022.
Article Dans Anglais | MEDLINE | ID: covidwho-1458806

Résumé

SARS-CoV-2 is a positive-sense RNA virus and it is the causative agent of the global COVID-19 outbreak. COVID-19 is similar to the previous outbreaks for instance SARS in 2002-2003 and MERS in 2012. As the peptides have many advantages, peptide-based therapeutics might be one of the possible ways in the development of COVID-19 specific drugs. SARS-CoV-2 enters into a human via its S protein by attaching with human hACE2 present on the cell membrane in the lungs and intestines of humans. hACE2 cleaves S protein into the S1 subunit for viral attachment and the S2 subunit for fusion with the host cell membrane. The fusion mechanism forms a six-helical bundle (6-HB) structure which finally fuses the viral envelope with the host cell membrane. hACE2 based peptides such as SBP1 and Spikeplug have shown their potential as antiviral agents. S protein-hACE2 interaction and the SARS-CoV-2 fusion machinery play a crucial part in human viral infection. It is evident that if these interactions could be blocked successfully and efficiently, it could be the way to find the drug for COVID-19. Several peptide-based inhibitors are potent inhibitors of S protein-hACE2 interaction. Similarly, the antiviral activity of the antimicrobial peptide, lactoferrin makes it an important candidate for the COVID-19 drug development process. A candidate drug, RhACE2-APN01 based on recombinant hACE2 peptide has already entered phase II clinical trials. This review sheds light on different aspects of the feasibility of using peptide-based therapeutics as the promising therapeutic route for COVID-19.


Sujets)
, Antiviraux/pharmacologie , Antiviraux/usage thérapeutique , Humains , Peptides/pharmacologie , Peptides/usage thérapeutique , SARS-CoV-2 , Glycoprotéine de spicule des coronavirus/composition chimique , Glycoprotéine de spicule des coronavirus/métabolisme
20.
researchsquare; 2021.
Preprint Dans Anglais | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-941184.v1

Résumé

Ever since the WHO's declaration of the SARS-CoV-2 pandemic, the medical literature has been focusing upon the patterns of association of SARS-CoV-2 with different diseases. Patients with Osler-Weber-Rendu Syndrome, also known as, Hereditary hemorrhagic telangiectasia (HHT), presents with recurrent epistaxis, nostril manipulations, incidental detection of multiple AVMs (Arterio-Venous Malformations), and telangiectasias over mucocutaneous tissues and internal organs. In addition, these AVMs are prone to bleed or act as a nidus for thrombus formation apart from other serious complications like chronic hypoxemia, anemia, pulmonary artery hypertension, heart failure, and cerebrovascular disease accidents. Here, we provide a case report of such a patient who was diagnosed with HHT as per 'Curaçao criteria'; having a history of multiple episodes of epistaxis, radiological evidence of AVMs over left calf, pulmonary and hepatic region, multiple telangiectasias in the splenic region and uterine vascular malformations. Upon acquiring severe COVID-19 infection, the patient developed complications like anemia, pulmonary artery hypertension, sepsis, acute kidney injury, and post COVID-19 persistence of type1 respiratory failure. Moreover, the risk-benefit ratio of anticoagulation therapy in such patients with COVID-19 infection is tricky and challenging; however, our patient was prophylactically anti-coagulated with enoxaparin for 12 days with an uneventful outcome. Keywords: Osler-Weber-Rendu Syndrome, Hereditary hemorrhagic telangiectasia, HHT, Prophylactic Anticoagulation, Covid-19, SARS-CoV-2.


Sujets)
Défaillance cardiaque , Télangiectasie hémorragique héréditaire , Anomalies vasculaires , Ataxie-télangiectasie , Fistule artérioartérielle , Angiopathies intracrâniennes , Hypoxie , Atteinte rénale aigüe , Anémie , COVID-19 , Insuffisance respiratoire
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