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2.
Front Genet ; 13: 1028081, 2022.
Article in English | MEDLINE | ID: covidwho-2260364

ABSTRACT

Background: Development and worldwide availability of safe and effective vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to fight severe symptoms of coronavirus disease 2019 (COVID-19) and block the pandemic have been a great achievement and stimulated researchers on understanding the efficacy and duration of different vaccine types. Methods: We investigated the levels of anti-SARS-CoV-2 antibodies (IgG) and neutralizing antibodies (NAbs) in 195 healthy adult subjects belonging to the staff of the University-Hospital of Ferrara (Italy) starting from 15 days up to 190 days (about 6 months) after the second dose of the BNT162b2 (Pfizer-BioNTech) mRNA-based vaccine (n = 128) or ChAdOx1 (AstraZeneca) adenovirus-based vaccine (n = 67) using a combined approach of serological and genomics investigations. Results: A strong correlation between IgG and NAb levels was detected during the 190 days of follow-up (r 2 = 0.807; p < 0.0001) and was confirmed during the first 90 days (T1) after vaccination (r 2 = 0.789; p = 0.0001) and 91-190 days (T2) after vaccination (r 2 = 0.764; p = 0.0001) for both vaccine types (r 2 = 0.842; p = 0.0001 and r 2 = 0.780; p = 0.0001 for mRNA- and adenovirus-based vaccine, respectively). In addition to age (p < 0.01), sex (p = 0.03), and type of vaccine (p < 0.0001), which partially accounted for the remarkable individual differences observed in the antibody levels and dynamics, interesting genetic determinants appeared as significant modifiers of both IgG and NAb responses among the selected genes investigated (TP53, rs1042522; APOE, rs7412/rs429358; ABO, rs657152; ACE2, rs2285666; HLA-A rs2571381/rs2499; CRP, rs2808635/rs876538; LZTFL1, rs35044562; OAS3, rs10735079; SLC6A20, rs11385942; CFH, rs1061170; and ACE1, ins/del, rs4646994). In detail, regression analysis and mean antibody level comparison yielded appreciable differences after genotype stratification (P1 and P2, respectively, for IgG and NAb distribution) in the whole cohort and/or in the mRNA-based vaccine in the following genes: TP53, rs1042522 (P1 = 0.03; P2 = 0.04); ABO, rs657152 (P1 = 0.01; P2 = 0.03); APOE, rs7412/rs429358 (P1 = 0.0018; P2 = 0.0002); ACE2, rs2285666 (P1 = 0.014; P2 = 0.009); HLA-A, rs2571381/rs2499 (P1 = 0.02; P2 = 0.03); and CRP, rs2808635/rs876538 (P1 = 0.01 and P2 = 0.09). Conclusion: High- or low-responsive subjects can be identified among healthy adult vaccinated subjects after targeted genetic screening. This suggests that favorable genetic backgrounds may support the progression of an effective vaccine-induced immune response, though no definite conclusions can be drawn on the real effectiveness ascribed to a specific vaccine or to the different extent of a genotype-driven humoral response. The interplay between data from the polygenic predictive markers and serological screening stratified by demogeographic information can help to recognize the individual humoral response, accounting for ethnic and geographical differences, in both COVID-19 and anti-SARS-CoV-2 vaccinations.

3.
Sci Total Environ ; : 160503, 2022 Nov 25.
Article in English | MEDLINE | ID: covidwho-2235687

ABSTRACT

Severe acute respiratory syndrome coronavirus 2, abbreviated as SARS-CoV-2, has been associated with the transmission of infectious COVID-19 disease through breathing and speech droplets emitted by infected carriers including asymptomatic cases. As part of SARS-CoV-2 global pandemic preparedness, we studied the transmission of aerosolized air mimicking the infected person releasing speech aerosol with droplets containing CorNPs using a vibrating mesh nebulizer as human patient simulator. Generally speech produces nanoaerosols with droplets of <5 µm in diameter that can travel distances longer than 1 m after release. It is assumed that speech aerosol droplets are a main element of the current Corona virus pandemic, unlike droplets larger than 5 m, which settle down within a 1 m radius. There are no systemic studies, which take into account speech-generated aerosol/droplet experimental validation and their aerodynamics/particle kinetics analysis. In this study, we cover these topics and explore role of residual water in aerosol droplet stability by exploring drying dynamics. Furthermore, a candle experiment was designed to determine whether air pollution might influence respiratory virus like nanoparticle transmission and air stability.

4.
Indian J Med Res ; 155(1): 123-128, 2022 01.
Article in English | MEDLINE | ID: covidwho-2201754

ABSTRACT

Background & objectives: The safety of the ChAdOx1 nCoV-19 vaccine is a cause of concern for many who have been vaccinated. The people have multiple concerns and fear regarding the adverse events of the vaccine. Thus, this study was undertaken to establish the safety profile of ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) among the healthcare professionals. Methods: This was a descriptive cross-sectional survey. After taking clearance from the institutional ethics committee 1500 healthcare professionals, who had their vaccination in the past two weeks were selected. They were provided with an online survey proforma regarding adverse events following immunization (AEFIs) of COVID-19 vaccine developed using google forms with an informed consent form affixed to it. Results: A total of 1036 individuals participated in the study. The mean and median (inter quartile range) age of the participants was 37.7 ±11.25 and 35 (29-46) yr, respectively. Of these, 52.1 per cent were female, 29.3 per cent were doctors, 33.4 per cent were nurses and 9.5 per cent were paramedical staff. Forty six per cent participants experienced one or more minor AEFIs such as pain, tenderness, redness, etc. at the injection site. Fatigue (31.75%), generalized feeling of unwell (28.57%), muscle pain (23.16%) and fever (21.71%) were the most commonly reported systemic AEFIs followed by headache (20.07%), dizziness (10.03%) and joint pains (15.25%). Most of them experienced these AEFIs within 24 h of the first dose of administration. About 42 per cent of the participants took oral antipyretics/analgesics for managing the AEFIs. Interpretation & conclusions: ChAdOx1 nCoV-19 Corona Virus Vaccine was found to be associated with mild local and systemic AEFIs that were more common after the first dose as compared to the second dose. There adverse events could be dealt with oral over-the-counter medications, with no requirement of hospitalization.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Cross-Sectional Studies , Delivery of Health Care , Female , Humans , Male
6.
Indian J Med Res ; 155(5&6): 526-537, 2022.
Article in English | MEDLINE | ID: covidwho-2040110

ABSTRACT

Background & objectives: The high mortality associated with the thrombotic events in hospitalized COVID-19 patients resulted in the usage of anticoagulants in varying doses. Whether high-dose anticoagulants have led to better outcomes or higher incidence of clinically significant bleeding events is debatable. Thus, this study was conducted to find the incidence of clinically significant bleeding events in moderate-to-severe COVID-19 ARDS (acute respiratory distress syndrome) patients on therapeutic anticoagulation and their outcomes. Methods: In this retrospective, single-centre study of 155 critically ill COVID-19 patients, the incidence of clinically significant bleeding was observed. Multivariate regression models were used to evaluate the association between anticoagulant regimen, coagulation and inflammatory markers with the incidence of bleeding and thrombotic events. Results: The incidence of clinically relevant non-major bleeding was 33.54 per cent (26.17-41.46%) and major bleeding was 9.03 per cent (5.02-14.69%). The anticoagulation intensity at baseline had a high odds of major bleeding when enoxaparin and dual antiplatelet therapy were used together [adjusted odds ratio OR of 434.09 (3.81-49502.95), P<0.05]. At admission, bleeders had a poorer PaO2/FiO2 ratio with more patients on invasive ventilation. At the time of bleeding, the bleeders had a higher D-dimer, ferritin, C-reactive protein and procalcitonin compared to non-bleeders. The subhazard ratio for death in bleeders was 3.35 (95% confidence interval, 1.97-5.65; P<0.001). Interpretation & conclusions: The incidence of bleeding in critically ill COVID-19 patients on therapeutic anticoagulation may increase with the severity of the disease as well as with concurrent use of dual antiplatelets. Major bleeding may also contribute to higher mortality.


Subject(s)
COVID-19 Drug Treatment , COVID-19 , Respiratory Distress Syndrome , Thrombosis , Humans , Anticoagulants , COVID-19/complications , Retrospective Studies , Critical Illness , Incidence , Hemorrhage/chemically induced , Hemorrhage/epidemiology
7.
J Anaesthesiol Clin Pharmacol ; 38(Suppl 1): S132-S133, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2024780
8.
Cells ; 11(17)2022 08 23.
Article in English | MEDLINE | ID: covidwho-2023201

ABSTRACT

Alcohol and several therapeutic drugs, including acetaminophen, are metabolized by cytochrome P450 2E1 (CYP2E1) into toxic compounds. At low levels, these compounds are not detrimental, but higher sustained levels of these compounds can lead to life-long problems such as cytotoxicity, organ damage, and cancer. Furthermore, CYP2E1 can facilitate or enhance the effects of alcohol-drug and drug-drug interactions. In this review, we discuss the role of CYP2E1 in the metabolism of alcohol and drugs (with emphasis on acetaminophen), mediating injury/toxicities, and drug-drug/alcohol-drug interactions. Next, we discuss various compounds and various nutraceuticals that can reduce or prevent alcohol/drug-induced toxicity. Additionally, we highlight experimental outcomes of alcohol/drug-induced toxicity and potential treatment strategies. Finally, we cover the role and implications of extracellular vesicles (EVs) containing CYP2E1 in hepatic and extrahepatic cells and provide perspectives on the clinical relevance of EVs containing CYP2E1 in intracellular and intercellular communications leading to drug-drug and alcohol-drug interactions. Furthermore, we provide our perspectives on CYP2E1 as a druggable target using nutraceuticals and the use of EVs for targeted drug delivery in extrahepatic and hepatic cells, especially to treat cellular toxicity.


Subject(s)
Cytochrome P-450 CYP2E1 , Extracellular Vesicles , Acetaminophen/pharmacology , Cytochrome P-450 CYP2E1/metabolism , Drug Interactions , Ethanol , Extracellular Vesicles/metabolism
9.
Children (Basel) ; 9(7)2022 Jul 12.
Article in English | MEDLINE | ID: covidwho-2002515

ABSTRACT

BACKGROUND: SARS-CoV-2 has affected millions of people around the world. There is a need for data on the effects of this infection on neonates admitted to neonatal intensive care (NICU) units born to infected mothers. Here, we decided to analyze neonates born to mothers who tested positive for SARS-CoV-2 and admitted to NICU compared with neonates who remained with their mothers. METHODS: All pregnant mothers who tested positive for SARS-CoV-2 during pregnancy between 1 June 2020 and 30 June 2021, along with all neonates born to infected pregnant women, were included in this study. We then compared the neonates admitted to NICU with the neonates who remained with their mothers. RESULTS: Eighty-eight neonates were born to eighty-eight SARS-CoV-2-positive mothers. Fifteen of these neonates were admitted to the NICU. The mothers of the neonates admitted to the NICU were more likely to have received prenatal care outside of the USA. In addition, the neonates admitted to the NICU were more likely to have needed significant resuscitation at birth. Respiratory distress was the most common reason for NICU admission. None of the NICU-admitted neonates were SARS-CoV-2-positive. There were no differences between the values of the complete blood counts, morbidities at discharge, lengths of hospitalization, or rates of readmission to hospital in the first month of life observed between the two groups. CONCLUSIONS: The vertical transmission of the SARS-CoV-2 infection remains rare; there was no difference in the hospital outcomes in the neonates of infected mothers. Unlike other studies, which show an increased tendency toward preterm birth in SARS-CoV-2-positive mothers, our study indicates no such association.

10.
Kidney360 ; 3(4): 728-733, 2022 04 28.
Article in English | MEDLINE | ID: covidwho-1955524

ABSTRACT

The coronavirus disease 2019 pandemic has had an unprecedented effect on health and health care and posed challenges to the conduct of clinical trials.Targeted mitigating strategies, on the basis of early and continued data collection from site surveys, limited disruption to the ASCEND trials.Flexibly allowing hemoglobin assessment at local laboratories to inform randomized treatment dosing was key to limiting the discontinuation of treatment.


Subject(s)
COVID-19 , Clinical Trials as Topic , Pandemics , COVID-19/epidemiology , Data Collection , Humans
11.
Hosp Top ; : 1-7, 2022 Jul 15.
Article in English | MEDLINE | ID: covidwho-1947775

ABSTRACT

Current study was conducted to assess the perception and barriers regarding proning among nurses. 385 nurses were conveniently surveyed using pre-tested tools. 3.9% of nurses "felt like running away" while providing care to the patients in prone position. 93.5% believed that prone position for COVID-19 patients is beneficial in reducing morbidity and that teamwork is required to be effective (96.6%). 93% nurses believed that inadequate staff-patient ratio is a significant barrier for prone positioning. Other barriers were fear of dislodgement of tubings (91.5%), difficulty in providing routine care (87.3%) and inadequate institutional protocol (83.9%). 12.5% were trained regarding proning.

12.
Lancet Reg Health Southeast Asia ; 3: 100023, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1945945

ABSTRACT

Background: Surge of SARS CoV-2 infections ascribed to omicron variant began in December 2021 in New Delhi. We determined the infection and reinfection density in a cohort of health care workers (HCWs) along with vaccine effectiveness (VE) against symptomatic infection within omicron transmission period (considered from December 01, 2021 to February 25, 2022. Methods: This is an observational study from the All India Institute of Medical Sciences, New Delhi. Data were collected telephonically. Person-time at risk was counted from November 30, 2021 till date of infection/ reinfection, or date of interview. Comparison of clinical features and severity was done with previous pandemic periods. VE was estimated using test-negative case-control design [matched pairs (for age and sex)]. Vaccination status was compared and adjusted odds ratios (OR) were computed by conditional logistic regression. VE was estimated as (1-adjusted OR)X100-. Findings: 11474 HCWs participated in this study. The mean age was 36⋅2 (±10⋅7) years. Complete vaccination with two doses were reported by 9522 (83%) HCWs [8394 (88%) Covaxin and 1072 Covishield (11%)]. The incidence density of all infections and reinfection during the omicron transmission period was 34⋅8 [95% Confidence Interval (CI): 33⋅5-36⋅2] and 45⋅6 [95% CI: 42⋅9-48⋅5] per 10000 person days respectively. The infection was milder as compared to previous periods. VE was 52⋅5% (95% CI: 3⋅9-76⋅5, p = 0⋅036) for those who were tested within 14-60 days of receiving second dose and beyond this period (61-180 days), modest effect was observed. Interpretation: Almost one-fifth of HCWs were infected with SARS CoV-2 during omicron transmission period, with predominant mild spectrum of COVID-19 disease. Waning effects of vaccine protection were noted with increase in time intervals since vaccination. Funding: None.

13.
Langmuir ; 38(26): 7976-7988, 2022 07 05.
Article in English | MEDLINE | ID: covidwho-1900415

ABSTRACT

The severity of global pandemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has engaged the researchers and clinicians to find the key features triggering the viral infection to lung cells. By utilizing such crucial information, researchers and scientists try to combat the spread of the virus. Here, in this work, we performed in silico analysis of the protein-protein interactions between the receptor-binding domain (RBD) of the viral spike protein and the human angiotensin-converting enzyme 2 (hACE2) receptor to highlight the key alteration that happened from SARS-CoV to SARS-CoV-2. We analyzed and compared the molecular differences between spike proteins of the two viruses using various computational approaches such as binding affinity calculations, computational alanine, and molecular dynamics simulations. The binding affinity calculations showed that SARS-CoV-2 binds a little more firmly to the hACE2 receptor than SARS-CoV. The major finding obtained from molecular dynamics simulations was that the RBD-ACE2 interface is populated with water molecules and interacts strongly with both RBD and ACE2 interfacial residues during the simulation periods. The water-mediated hydrogen bond by the bridge water molecules is crucial for stabilizing the RBD and ACE2 domains. Near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) confirmed the presence of vapor and molecular water phases in the protein-protein interfacial domain, further validating the computationally predicted interfacial water molecules. In addition, we examined the role of interfacial water molecules in virus uptake by lung cell A549 by binding and maintaining the RBD/hACE2 complex at varying temperatures using nanourchins coated with spike proteins as pseudoviruses and fluorescence-activated cell sorting (FACS) as a quantitative approach. The structural and dynamical features presented here may serve as a guide for developing new drug molecules, vaccines, or antibodies to combat the COVID-19 pandemic.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Spike Glycoprotein, Coronavirus , Water , A549 Cells , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , COVID-19/virology , Humans , Molecular Dynamics Simulation , Pandemics , Peptidyl-Dipeptidase A/metabolism , Protein Binding , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Water/chemistry
14.
Smart Health (Amst) ; 25: 100296, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1886079

ABSTRACT

Given the novel corona virus discovered in Wuhan, China, in December 2019, due to the high false-negative rate of RT-PCR and the time-consuming to obtain the results, research has proved that computed tomography (CT) has become an auxiliary One of the essential means of diagnosis and treatment of new corona virus pneumonia. Since few COVID-19 CT datasets are currently available, it is proposed to use conditional generative adversarial networks to enhance data to obtain CT datasets with more samples to reduce the risk of over fitting. In addition, a BIN residual block-based method is proposed. The improved U-Net network is used for image segmentation and then combined with multi-layer perception for classification prediction. By comparing with network models such as AlexNet and GoogleNet, it is concluded that the proposed BUF-Net network model has the best performance, reaching an accuracy rate of 93%. Using Grad-CAM technology to visualize the system's output can more intuitively illustrate the critical role of CT images in diagnosing COVID-19. Applying deep learning using the proposed techniques suggested by the above study in medical imaging can help radiologists achieve more effective diagnoses that is the main objective of the research. On the basis of the foregoing, this study proposes to employ CGAN technology to augment the restricted data set, integrate the residual block into the U-Net network, and combine multi-layer perception in order to construct new network architecture for COVID-19 detection using CT images. -19. Given the scarcity of COVID-19 CT datasets, it is proposed that conditional generative adversarial networks be used to augment data in order to obtain CT datasets with more samples and therefore lower the danger of overfitting.

15.
Comput Biol Med ; 146: 105419, 2022 07.
Article in English | MEDLINE | ID: covidwho-1803804

ABSTRACT

Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the vaccine effectiveness. Asymptomatic breakthrough infections have been a major problem in assessing vaccine effectiveness in populations globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines since whole virion vaccines generate antibodies against all the viral proteins. Here, we show how a statistical and machine learning (ML) based approach can be used to discriminate between SARS-CoV-2 infection and immune response to an inactivated whole virion vaccine (BBV152, Covaxin). For this, we assessed serial data on antibodies against Spike and Nucleocapsid antigens, along with age, sex, number of doses taken, and days since last dose, for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, our ensemble ML model classified 724 to be infected. For method validation, we determined the relative ability of a random subset of samples to neutralize Delta versus wild-type strain using a surrogate neutralization assay. We worked on the premise that antibodies generated by a whole virion vaccine would neutralize wild type more efficiently than delta strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, neutralization against Delta strain was more effective, indicating infection. We found 71.8% subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period. Our approach will help in real-world vaccine effectiveness assessments where whole virion vaccines are commonly used.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Humans , Machine Learning , Pandemics , SARS-CoV-2 , Vaccines, Inactivated , Virion
16.
Infect Genet Evol ; 99: 105260, 2022 04.
Article in English | MEDLINE | ID: covidwho-1773643

ABSTRACT

The ongoing pandemic that resulted from coronavirus disease (COVID-19), which is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), had been spiraling out of control with no known antiviral drugs or vaccines. Due to the extremely serious nature of the disease, it has claimed many lives, with a mortality rate of 3.4% declared by the World Health Organization (WHO) on March 3, 2020. The aim of this study is to gain an understanding of the regulatory nature of the proteins involved in COVID-19 and to explore the possibility that microRNA (miRNA) could become a major component in the decoding of the virus. In the study, we were able to correlate the host protein gene BCL2L1 with miRNA miR-23b via network analysis. MiRNAs have previously been associated with the antiviral properties of various viral diseases, such as enterovirus 71 and hepatitis. They have been reported to act as antiviral regulators, since they are an integral component in the direct regulation of viral genes. MiRNAs are also capable of enabling the virus to avoid the host immune response by suppressing the IFN-α/ß signaling pathway or increasing the production of IFN-α/ß and as a result, inhibiting the viral infection. Here, we explain and shed light on the various correlations in the miRNA-gene-disease association that are seen in the host proteins of COVID-19.


Subject(s)
COVID-19 , MicroRNAs , Humans , MicroRNAs/genetics , Pandemics , Prevalence , SARS-CoV-2/genetics , bcl-X Protein
17.
International Management Review ; 18:79-90,93-94, 2022.
Article in English | ProQuest Central | ID: covidwho-1762416

ABSTRACT

Information and communication technology (ICT) advancement has created a plethora of opportunities for several business sectors, especially the industries that include star-classified Indian and international hotels. However, several business areas lack the required support system (digital challenges) for such areas as lack of education, training, and the capacity for building up of local people. Hoteliers promoting hotel rooms mimic home-based rooms are almost gone;it is just not feasible to keep up due to rapid changes in technology. It was observed that a hotel's tech cycle is much speedier than its refurbishment cycle. This research study was conducted in order to discuss the top 16 digital marketing challenges and their best possible solutions in the international hotel industry. The study's objective was to explore the digital sustainability for star-classified Indian and internationally classified hotels in the COVID-19 pandemic. The study was qualitative and explorative in nature.

18.
Sci Rep ; 12(1): 2145, 2022 02 09.
Article in English | MEDLINE | ID: covidwho-1692555

ABSTRACT

The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been studied. In the present study, we have assessed in vitro enzymatic inhibitory activity of active ingredients in the oral mouth rinse products: aloin A and B, chlorhexidine, eucalyptol, hexetidine, menthol, triclosan, methyl salicylate, sodium fluoride and povidone, against two important proteases of SARS-CoV-2 PLpro and 3CLpro. Our results indicate only aloin A and B effectively inhibited proteolytic activity of PLpro with an IC50 of 13.16 and 16.08 µM. Interestingly, neither of the aloin isoforms inhibited 3CLpro enzymatic activity. Computational structural modelling of aloin A and B interaction with PLpro revealed that, both aloin isoforms form hydrogen bond with Tyr268 of PLpro, which is critical for their proteolytic activity. Furthermore, 100 ns molecular dynamics (MD) simulation studies predicted that both aloin isoforms have strong interaction with Glu167, which is required for PLpro deubiquitination activity. Our results from the in vitro deubiquitinase inhibition assay show that aloin A and B isomers exhibit deubiquitination inhibitory activity with an IC50 value of 15.68 and 17.51 µM, respectively. In conclusion, the isoforms of aloin inhibit both proteolytic and the deubiquitinating activity of SARS-CoV-2 PLpro, suggesting potential in inhibiting the replication of SARS-CoV-2 virus.


Subject(s)
Coronavirus Papain-Like Proteases/metabolism , Emodin/analogs & derivatives , SARS-CoV-2/enzymology , Animals , Binding Sites , COVID-19/pathology , COVID-19/virology , Cell Survival/drug effects , Chlorocebus aethiops , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/metabolism , Coronavirus Papain-Like Proteases/antagonists & inhibitors , Emodin/chemistry , Emodin/metabolism , Emodin/pharmacology , Humans , Molecular Dynamics Simulation , Protein Isoforms/chemistry , Protein Isoforms/metabolism , Protein Isoforms/pharmacology , SARS-CoV-2/isolation & purification , Vero Cells
19.
Biology (Basel) ; 11(2)2022 Jan 23.
Article in English | MEDLINE | ID: covidwho-1650047

ABSTRACT

People living with HIV/AIDS (PLWHA) are at an increased risk of severe and critical COVID-19 infection. There is a steady increase in neurological complications associated with COVID-19 infection, exacerbating HIV-associated neurocognitive disorders (HAND) in PLWHA. Nutraceuticals, such as phytochemicals from medicinal plants and dietary supplements, have been used as adjunct therapies for many disease conditions, including viral infections. Appropriate use of these adjunct therapies with antiviral proprieties may be beneficial in treating and/or prophylaxis of neurological complications associated with these co-infections. However, most of these nutraceuticals have poor bioavailability and cannot cross the blood-brain barrier (BBB). To overcome this challenge, extracellular vesicles (EVs), biological nanovesicles, can be used. Due to their intrinsic features of biocompatibility, stability, and their ability to cross BBB, as well as inherent homing capabilities, EVs hold immense promise for therapeutic drug delivery to the brain. Therefore, in this review, we summarize the potential role of different nutraceuticals in reducing HIV- and COVID-19-associated neurological complications and the use of EVs as nutraceutical/drug delivery vehicles to treat HIV, COVID-19, and other brain disorders.

20.
JAMA Netw Open ; 5(1): e2142210, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1611175

ABSTRACT

Importance: A surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021. Objective: To assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection. Design, Setting, and Participants: This was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India. Exposures: Vaccination with 0, 1, or 2 doses of BBV152. Main Outcomes and Measures: The HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 - adjusted HR) was reported. Results: Among 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection. Conclusions and Relevance: These findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.


Subject(s)
COVID-19/epidemiology , Health Personnel , Reinfection , SARS-CoV-2 , Adult , COVID-19/etiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Cohort Studies , Female , Humans , Immunogenicity, Vaccine , India/epidemiology , Male , Middle Aged , Surveys and Questionnaires , Tertiary Care Centers , Vaccines, Inactivated/administration & dosage , Virion/immunology , Young Adult
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