ABSTRACT
The current global health crisis caused by the SARS-CoV-2 virus (COVID-19) has increased the use of personal protective equipment, especially face masks, leading to the disposal of a large amount of plastic waste causing an environmental crisis due to the use of non-biodegradable and non-recyclable polymers, such as polypropylene and polyester. In this work, an eco-friendly biopolymer, polylactic acid (PLA), was used to manufacture hierarchical nanoporous microfiber biofilters via a single-step rotary jet spinning (RJS) technique. The process parameters that aid the formation of nanoporosity within the microfibers were discussed. The microstructure of the fibers was analyzed by scanning electron microscopy (SEM) and a noninvasive X-ray microtomography (XRM) technique was employed to study the three-dimensional (3D) morphology and the porous architecture. Particulate matter (PM) and aerosol filtration efficiency were tested by OSHA standards with a broad range (10-1000 nm) of aerosolized saline droplets. The viral penetration efficiency was tested using the phi X174 bacteriophage (similar to 25 nm) with an envelope, mimicking the spike protein structure of SARS-CoV-2. Although these fibers have a similar size used in N95 filters, the developed biofilters present superior filtration efficiency (similar to 99%) while retaining better breathability (<4% pressure drop) than N95 respirator filters.
ABSTRACT
The current global health crisis caused by the SARS-CoV-2 virus (COVID-19) has increased the use of personal protective equipment, especially face masks, leading to the disposal of a large amount of plastic waste causing an environmental crisis due to the use of non-biodegradable and non-recyclable polymers, such as polypropylene and polyester. In this work, an eco-friendly biopolymer, polylactic acid (PLA), was used to manufacture hierarchical nanoporous microfiber biofilters via a single-step rotary jet spinning (RJS) technique. The process parameters that aid the formation of nanoporosity within the microfibers were discussed. The microstructure of the fibers was analyzed by scanning electron microscopy (SEM) and a noninvasive X-ray microtomography (XRM) technique was employed to study the three-dimensional (3D) morphology and the porous architecture. Particulate matter (PM) and aerosol filtration efficiency were tested by OSHA standards with a broad range (10-1000 nm) of aerosolized saline droplets. The viral penetration efficiency was tested using the ΦX174 bacteriophage (∼25 nm) with an envelope, mimicking the spike protein structure of SARS-CoV-2. Although these fibers have a similar size used in N95 filters, the developed biofilters present superior filtration efficiency (∼99%) while retaining better breathability (<4% pressure drop) than N95 respirator filters. © 2023 American Chemical Society
ABSTRACT
Background: Three or more waves of COVID 19 pandemic have hit the different parts of world including India very hard, taking toll on the lives of people both in terms of morbidity and mortality. Keeping this in mind, the present study was conducted with an aim to determine the socio-demographic and clinical profile of laboratory confirmed COVID 19 cases and to determine their association with oxygen requirement and outcome of disease at the time of discharge. Methods: The present cross-sectional study was conducted on lab confirmed COVID 19 cases admitted in tertiary care hospital in Jammu from June-July 2021. Data was collected using convenient sampling method. The self-designed questionnaire used for data collection obtained information regarding socio-demographic characteristics of patients as well as clinical features of the disease. Results: Out of total 161 patients studied, 60.8% were males and 39.2% were females. Mean age was 51.2 .. 17.5 years. Comorbid conditions were present in 37.8% patients, with hypertension being the most common (36%). Cough, Fever, breathlessness and myalgia were the main presenting symptoms (90%, 81%, 57.7% and 56% respectively). The variables which were found to have statistically significant association with oxygen requirement and the outcome of disease at the time of discharge were age, gender and presence of co-morbidity (p <0.05). Conclusions: Advancing age, male gender and presence of underlying co-morbidity were found to be significant risk factors for the requirement of oxygen and poor outcome of the disease.
ABSTRACT
Background: Three or more waves of COVID 19 pandemic have hit the different parts of world including India very hard, taking toll on the lives of people both in terms of morbidity and mortality. Keeping this in mind, the present study was conducted with an aim to determine the socio-demographic and clinical profile of laboratory confirmed COVID 19 cases and to determine their association with oxygen requirement and outcome of disease at the time of discharge. Methods: The present cross-sectional study was conducted on lab confirmed COVID 19 cases admitted in tertiary care hospital in Jammu from June-July 2021.Data was collected using convenient sampling method. The self-designed questionnaire used for data collection obtained information regarding socio-demographic characteristics of patients as well as clinical features of the disease. Results: Out of total 161 patients studied, 60.8% were males and 39.2% were females. Mean age was 51.2 +/- 17.5 years. Comorbid conditions were present in 37.8% patients, with hypertension being the most common ( 36%). Cough, Fever, breathlessness and myalgia were the main presenting symptoms (90%, 81%, 57.7% and 56% respectively). The variables which were found to have statistically significant association with oxygen requirement and the outcome of disease at the time of discharge were age, gender and presence of co-morbidity (p <0.05). Conclusions: Advancing age, male gender and presence of underlying co-morbidity were found to be significant risk factors for the requirement of oxygen and poor outcome of the disease.
ABSTRACT
Introduction: Infection-related IgA glomerulonephritis with large paramesangial immune deposits appearing like intraluminal cryo deposits have occasionally been described in literature temporally associated with Staphylococcus infection. COVID-19 associated glomerular disease is classically known to manifest as collapsing glomerulopathy, although other types have been reported. Case Description: We present a case of a 76-year old Hispanic female with a history of type 2 diabetes, hypertension and a 2-month old history of COVID-19 pneumonia who recently presented with acute kidney injury, dark urine, shortness of breath and leg edema. 2 weeks prior, she had presented with a history of purpuric rash. Urinalysis had shown hematuria and proteinuria, and a skin biopsy showed IgA vasculitis. Blood culture for Staphylococcus was negative. A kidney biopsy now showed IgA glomerulonephritis with focal crescents along with intraluminal pseudothrombi (cryo-plugs) positive for IgA on immunofluorescence. Electron microscopy showed intraluminal occlusive electron-dense deposits. Serum cryoglobulin was negative. The patient was treated with steroids and oral cyclophosphamide, and she responded significantly to treatment. Discussion(s): Our case shows a unique glomerular manifestation of COVID-19 infection in the form of IgA vasculitis with intraluminal cryo-like features, not previously described in literature.
ABSTRACT
Introduction: Vaccines revolutionised the management of COVID19. Nevertheless, they lack efficacy in high-risk or vulnerable groups (e.g., immunosuppressed patients), who may not mount an appropriate immune response. Monoclonal antibodies represent the gold-standard agents for such cases;but they are limited by availability, need for parenteral administration and the risk for viral escape because of spike protein mutations. Therefore, there is a pressing need for new prophylactic agents less prone to resistance.The viral receptor ACE2 represents an ideal target as it is essential for viral entry and transmission and because being a host protein it is not affected by viral mutations. However, the regulation of ACE2 remains elusive, due to the lack of appropriatein vitromodels. Cholangiocytes show one of the highest ACE2 expression levels in the body, representing an ideal platform for these studies. Here, we use cholangiocyte organoids as proof-of-principleto identify that the bile acid receptor FXR regulates ACE2 expression and SARS-CoV-2 infectionin vitro. We validate these findings in lung and gut organoids, animal models, human organs perfusedex situand patient cohorts. Aims & Methods: 1. Identify pathways controlling the transcriptional regulation of ACE2 2. Identify drugs modulating these pathways as novel prophylactic and therapeutic agents for COVID19. Organoids were propagated using established protocols. Marker expression was assessed using single-cell RNA sequencing, QPCR, and immunofluorescence. FXR binding on DNA was assessed with chromatin immunoprecipitation. SARS-CoV-2 was isolated from bronchoalveolar lavage of a COVID19 patient. Syrian golden hamsters were infected via direct inoculation and QPCR on oral swab, nasal turbinate and lung samples was used to measure SARS-CoV-2 infection. Human livers and lungs not used for transplantation were perfusedex-situusing normothermic perfusion. Nasopharyngeal swabs were used to measure ACE2 expression in nasal epithelial cells of healthy individuals taking UDCA at the standard therapeutic dose of 15 mg/kg/day. Patient registry data were compared using propensity score matching for sex, age, diabetes, NAFLD and Child- Turcotte-Pugh score. Result(s): We identified that FXR directly regulates ACE2 transcription in cholangiocyte organoids, while FXR inhibition with the approved drug ursodeoxycholic acid (UDCA), reduced ACE2 expression and SARS-CoV-2 infectionin vitro. We confirmed this mechanism in organoids from other COVID19-affected tissues, including the respiratory and intestinal systems. We validated our findingsin vivoin Syrian golden hamsters, showing that treatment with UDCA downregulates ACE2 and prevents SARS-CoV-2 infection. We confirmed that UDCA reduces ACE2 and SARS-CoV-2 infection in human lungs and livers perfusedex-situ. We performed a clinical study demonstrating that UDCA lowers ACE2 levels in the nasal epithelium of 6 healthy volunteers. Finally, we identified a correlation between UDCA and better clinical outcomes (hospitalisation, ICU admission and death) in COVID19 patients receiving UDCA for cholestatic diseases using the COVID-Hep and SECURELiver registry data. Conclusion(s): We identified FXR as a novel regulator of ACE2 expression. Using a bench-to-bedside approach combining in vitroand in vivomodels, exsituperfused human organs and clinical data we showed that FXR inhibition prevents or reduces SARS-CoV-2 infection and identified UDCA as an approved, cost-effective drug which could be repurposed for COVID19, paving the road for future clinical trials.
ABSTRACT
COVID-19 is a recently discovered highly communicable disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) and its variants. The sudden emergence of the COVID 19 pandemic and its impact on global health meant that the development of effective and safe vaccines was crucial for this new lethal disease as vaccination always plays an essential role in the advancement of global health. So far, there are three main types of COVID-19 vaccines in use around the world: mRNA-based vaccines, adenoviral vector vaccines, and inactivated whole-virus vaccines. Since the introduction of vaccines for the COVID-19 disease, various reports of a spectrum of mucocutaneous side effects have surfaced. With the aid of this case series we would like to highlight the different types of cutaneous adverse effects that were observed post vaccination with the COVISHIELDTM vaccine by the department of Dermatology at our institution. Copyright © 2022, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.
ABSTRACT
The outbreak of COVID-19 has triggered a fall in the pandemic has completely changed the worldandtransformedour lives, the patterns of economies, and the behaviour of businesses. The market has the tendency to perceive long-term shocks which economy can give to the market, but contrary to generalization, short-term shocks are more vulnerable. The objective of the study was to provide an overview of the impact of the 'Outbreak of COVID-19 Pandemic Shockwaves on the returns and volatility of Thailand and Indian Stock Market. It also analysed whether both countries were reacting similarly to the pandemic. The data was divided into three categories, i.e. Before COVID-19 pandemic, During COVID-19 pandemic and the Whole Period collectively. The 'Pre-Pandemic Time Period' was taken from 1st July 2019 to 31st January 2020, 'During Pandemic Time Period' from 1st February 2020 to 31st August 2020 and the 'Whole Time Period' from 1st July 2019 to 31st August 2020. Three Stock Exchange Indices of both markets were monitored in the study. The standard GARCH models like GARCH, EGARCH, TGARCH, and PARCH models were used to assess the volatility of both markets. The study revealed that the negative shocks had greateraimpact on these markets than the positive shocks during the pandemic period. However, most of the parameter estimates were found to be statistically significant in all models, which meant there was the presence of leverage effect in returns of both stock markets. © 2022 Thammasat University. All Rights Reserved.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), has been responsible for a respiratory tract disease which has taken the proportion of the pandemic (COVID-19) ravaging the planet for last 2 and half year. The COVID-19 pandemic has been responsible for about sixty-one million deaths and about 500 million infections worldwide. The medication of infected individuals has been mainly cantered around repurposing of available known antiviral drugs, immunosuppressor/ immunomodulator drugs, monoclonal antibody concoctions and various vaccines as prophylaxis measures. Use phytometabolites in studies have been found to very effective in counter the SARS-CoV-2 spike protein binding sites, the main step to virus attack on the respiratory epithelial cells. Lichen secondary metabolites are well known for their antimicrobial, immunomodulator and antiviral activities. Current study was done to assess the spike protein binding capabilities of some lichen secondary metabolites of SARS-CoV-2 (Wuhan strain) spike protein binding sites using in-silico docking modelling. The study found that some of the lichen metabolites such as Cryptostictic acid and Quaesitic acid were effective in blocking the target cell recognising regions of the SARS-CoV-2 spike protein and can be effectively developed as therapeutic medicine.
ABSTRACT
Background & Objective: Neurological manifestations of novel-coronavirus disease (COVID-19) have been described in various studies. None of these studies has compared the findings in COVID-19 patients with COVID-negative patients presenting with similar clinical symptomatology during the same period. We undertook this case-control study with an aim to establish a direct relationship between COVID-19 infection and CNS related clinical and imaging presentations. Methods: This study was a review of retrospectively collected data of the patients who presented with different neurological symptoms to a tertiary care hospital in India. Based on results of Reverse transcriptase-polymerase chain reaction for SARS-Co-V-2, patients were classified into COVID-19 positive and COVID-19 negative groups. MRI findings in both groups were reviewed for acute ischemic stroke, intracranial bleed and other acute imaging abnormalities. Basic demographic information and stroke-related co-morbidities were also compared. Results: Eighty four patients in COVID-19 positive group and 323 patients in COVID-19 negative group underwent brain MRI for acute neurological symptoms during the same period. There was no statistically significant difference in presenting symptoms, sex distribution and risk factors for stroke. There was a higher prevalence of increased coagulability in COVID-19 positive group (p-value = 0.009). No statistically significant association was observed for infarcts or their hemorrhagic transformation, intracranial bleed, intracranial infection or dural sinus thrombosis. An association was found between acute diffuse leukoencephalopathy and COVID-19 infection (p value < 0.05). Conclusion: The current study points towards a weak direct association between COVID-19 infection and acute abnormalities in MRI brain studies, especially in patients with pre-existing co-morbidities.
ABSTRACT
Currently, the entire world is fighting against the Corona Virus (COVID-19). As of now, more than thirty lacs of people all over the world were died due to the COVID-19 till April 2021. A recent study conducted by China suggests that Chest CT and X-ray images can be used as a preliminary test for COVID detection. This paper propose a transfer learning-based mathematical COVID detection model, which integrates a pre-trained model with the Random Forest Tree (RFT) classifier. As the available COVID dataset is noisy and imbalanced so Principal Component Analysis (PCA) and Generative Adversarial Networks (GANs) is used to extract most prominent features and balance the dataset respectively. The Bayesian Cross-Entropy Loss function is used to penalize the false detection differently according to the class sensitivity (i.e., COVID patient should not be classified as Normal or Pneumonia class). Due to the small dataset, a pre-trained model like VGGNet-19, ResNet50 and Inception_ResNet_V2 were chosen to extract features and then trained them over the RFT for the classification task. The experiment results showed that ResNet50 gives the maximum accuracy of 99.51%, 98.21%, and 97.2% for training, validation, and testing phases, respectively, and none of the COVID Chest X-ray images were classified as Normal or Pneumonia classes.
ABSTRACT
Background: Despite recent advances, the management of COVID19 is complicated by vaccine availability, the modest efficacy of existing treatments, and the potential for viral resistance. Therefore, there is a pressing need for new prophylactic and therapeutic agents. Modifying the expression of the SARS-CoV-2 entry receptor ACE2 could prevent viral infection and limit disease progression. Here, we identify that ACE2 expression is controlled by the transcription factor farnesoid X receptor (FXR) and demonstrate that ACE2 downregulation through FXR antagonism, using approved drugs, such as ursodeoxycholic acid (UDCA), could represent a novel therapeutic strategy to complement current approaches. Methods: Primary cholangiocyte, pulmonary and intestinal organoids were propagated using established protocols. Marker expression was assessed using singlecell RNA sequencing, QPCR, immunofluorescence and flow cytometry. FXR binding on DNA was assessed with chromatin immunoprecipitation. SARS-CoV-2 was isolated from bronchoalveolar lavage of a COVID19 patient. Viral load was measured via QPCR. Human livers not used for transplantation were perfused ex-situ using the metra (OrganOx) normothermic perfusion device. Serum ACE2 activity was measured with commercial kits. Patient data from the COVID-Hep and SECURE-Liver registries were compared using propensity score matching. Results: FXR activation directly upregulated ACE2 transcription in organoids from COVID19 affected tissues, including the biliary, gastrointestinal and respiratory systems. Conversely, FXR antagonism with z-guggulsterone or UDCA, had the opposite effect. Importantly, both drugs reduced susceptibility to SARS-CoV-2 infection in lung, cholangiocyte and gut organoids. Furthermore, systemic administration of UDCA in human organs perfused ex-situ downregulated ACE2 and reduced SARS-CoV-2 infection ex-vivo. Oral UDCA rapidly reduced serum ACE2 in vivo. Registry data showed a correlation between UDCA administration and better clinical outcomes in COVID19 patients, including hospitalisation, ICU admission, mechanical ventilation and death. Conclusion: We discovered FXR as a novel therapeutic target against SARS-CoV-2 and we identified approved FXR inhibitors which could be repurposed to potentially treat COVID19, paving the road for future clinical trials to validate these results.
ABSTRACT
The Covid-19 pandemic since 2019 has imparted a massive influence on the human life around the world, irrespective of all the precautionary measures followed worldwide it is strongly suggested that only the effective and safer vaccine can control this vicious pandemic. Nevertheless, the vaccine development strategies for Covid-19 was initiated firstly in china after the outbreak of Covid-19 and then globally after it was declared as pandemic by World Health Organization. Currently, numerous platforms have been designed for developing the most efficacious and safe vaccines designed by different technologies including protein subunit, viral vector, RNA, DNA, inactivated, and live attenuated approach. Here, this review will illustrates the detailed information on above mentioned Covid-19 vaccines development technologies, protocols and their clinical trial phase status. Additionally, this review also includes the details of vaccines failed to progress further.
ABSTRACT
Introduction The management of COVID19 is complicated by vaccine availability, the modest efficacy of existing treatments, and the potential for viral resistance. Therefore, there is a pressing need for new prophylactic and therapeutic agents. The viral receptor ACE2 is an ideal target as it is required for SARS-CoV-2 entry in host cells. Modifying ACE2 expression could prevent infection and/or limit disease progression. Nevertheless, the mechanisms controlling ACE2 expression remain elusive. Aims To identify pathways controlling the transcriptional regulation of ACE2, and exploit them to reduce SARS-CoV-2 infection. Methods Organoids from primary biliary, intestinal and pulmonary epithelia were derived and cultured as previously described. Single-cell RNA sequencing, QPCR, immunofluorescence and flow cytometry were used to assess marker expression. Chromatin immunoprecipitation was used to assess FXR binding on DNA. Bronchoalveolar lavage SARS-CoV-2 patient isolates were used for infection experiments. Human livers not used for transplantation were connected to the metra (OrganOx) normothermic perfusion device and perfused ex-situ using therapeutic doses of UDCA for 12 hours. ACE2 activity was measured following manufacturer's instructions. Patient data from the COVID-Hep and SECURE-Liver registries were compared using propensity score matching for sex, age and Child-Turcotte-Pugh score. Results We first demonstrated that cholangiocytes are susceptible to SARS-CoV-2 infection in vivo and in organoid culture. We then used cholangiocyte organoids to identify FXR as a transcriptional regulator of ACE2. We validated our results in pulmonary and intestinal organoids, showing that ACE2 regulation by FXR represents a broad mechanism present in multiple COVID19-affected tissues. We then demonstrated that approved FXR inhibitors, such as ursodeoxycholic acid (UDCA) and z-guggulsterone (ZGG), decrease ACE2 levels and reduce viral infection in vitro in primary biliary, intestinal and pulmonary organoids. We interrogated the impact of systemic UDCA administration in human livers perfused ex-situ, demonstrating reduced ACE2 levels and SARS-CoV-2 infection. Furthermore, we showed that commencing UDCA treatment lowers ACE2 levels in primary biliary cholangitis (PBC) patients. Finally, we identified a correlation between UDCA treatment and better clinical outcome in COVID-19 patients, including hospitalisation, ICU admission, mechanical ventilation and death, using registry data. Conclusion We identified FXR as a novel master regulator of ACE2 expression. Using a bench-to-bedside approach we combined in vitro, ex-vivo and patient data to demonstrate the efficacy of ACE2 downregulation against SARS-CoV-2 infection and identified approved and inexpensive drugs (UDCA, ZGG) which could be repurposed as prophylactic and therapeutic agents against SARS-CoV-2 infection, paving the road for future clinical trials.
ABSTRACT
The present study deals with the impact of the pandemic outbreak of COVID-19 on the ambient air quality in the capital city of India. Real-time data were collected from eight continuous ambient air quality monitoring stations measuring important air quality parameters (NO2, PM10 and PM2.5). Results revealed that the city's air quality had improved significantly during the lockdown period due to COVID-19 outbreak. The concentration of gaseous and particulate matter during the lockdown period (March-May 2020) declined significantly compared with the preceding years' data from the same timeframe. However, the ambient air quality deteriorates with the onset of unlocking phases and post-monsoon season (October 2020). Higher concentration of NO2, PM10 and PM2.5 were recorded at industrial (S1 and S2) and hotspot (S4 and S5) sites. The lowest concentrations of studied pollutants were observed during the first phase of lockdown (March 24 - May 14, 2020). The present study, once again, establishes the direct effect of anthropogenic activities and deteriorating ambient air quality of Delhi.