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1.
Heliyon ; 8(10): e10893, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2061201

ABSTRACT

Environmental sustainability is essential in tourism literature, and sun-and-beach tourism (SBT) is one of the most popular subsections of the tourism field. The appropriate policies and strategies during the COVID-19 pandemic to revive SBT growth through the lens of the regulatory dimension (RED) and risk dimension (RID) of environmental sustainability are gaining timely ground to conduct this research. The current study examined the nexus between SBT, RED, and RID utilizing three novel indexes (i.e., weighted sun-and-beach tourism index, weighted regulatory dimension index, and weighted risk dimension index) by employing the principal component analysis within the framework of six stages of empirical estimation strategy. These three novel indexes combine the most commonly used SBT, RED, and RID indicators. This research tested the CSD and homogeneous, then employed the second generation CIPS-CADF panel unit root test, used an AMG estimator, and employed the panel Toda-Yamamoto (PTY) causality test. The findings revealed that the RED positively influences SBT while the RID mitigates SBT. Results also indicate bidirectional causality between SBT, RID, and RED. In other words, changes in RID and RED have predictive power for the SBT, which further highlights the role of SBT on the RID and RED. Therefore, concerned authorities can focus on environmental sustainability design initiatives and appropriate policy/strategy implications to boost SBT.

2.
Health Policy Plan ; 37(8): 979-989, 2022 Sep 13.
Article in English | MEDLINE | ID: covidwho-2051393

ABSTRACT

Decentralized, person-centred models of care delivery for drug-resistant tuberculosis (DR-TB) continue to be under-resourced in high-burden TB countries. The implementation of such models-made increasingly urgent by the COVID-19 pandemic-are key to addressing gaps in DR-TB care. We abstracted data of rifampicin-resistant (RR)/multidrug-resistant tuberculosis (MDR-TB) patients initiated on treatment at 11 facilities between 2010 and 2017 in Sindh and Balochistan provinces of Pakistan. We analysed trends in treatment outcomes relating to programme expansion to peri-urban and rural areas and estimated driving distance from patient residence to treatment facility. Among the 5586 RR/MDR-TB patients in the analysis, overall treatment success decreased from 82% to 66% between 2010 and 2017, as the programme expanded. The adjusted risk ratio for unfavourable outcomes was 1.013 (95% confidence interval 1.005-1.021) for every 20 km of driving distance. Our analysis suggests that expanding DR-TB care to centralized hubs added to increased unfavourable outcomes for people accessing care in peri-urban and rural districts. We propose that as enrolments increase, expanding DR-TB services close to or within affected communities is essential.


Subject(s)
COVID-19 , Tuberculosis, Multidrug-Resistant , Antitubercular Agents/therapeutic use , Humans , Pakistan , Pandemics , Politics , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology
3.
Int J Mol Sci ; 23(18)2022 Sep 07.
Article in English | MEDLINE | ID: covidwho-2010120

ABSTRACT

During the past two decades, the world has witnessed the emergence of various SARS-CoV-2 variants with distinct mutational profiles influencing the global health, economy, and clinical aspects of the COVID-19 pandemic. These variants or mutants have raised major concerns regarding the protection provided by neutralizing monoclonal antibodies and vaccination, rates of virus transmission, and/or the risk of reinfection. The newly emerged Omicron, a genetically distinct lineage of SARS-CoV-2, continues its spread in the face of rising vaccine-induced immunity while maintaining its replication fitness. Efforts have been made to improve the therapeutic interventions and the FDA has issued Emergency Use Authorization for a few monoclonal antibodies and drug treatments for COVID-19. However, the current situation of rapidly spreading Omicron and its lineages demands the need for effective therapeutic interventions to reduce the COVID-19 pandemic. Several experimental studies have indicated that the FDA-approved monoclonal antibodies are less effective than antiviral drugs against the Omicron variant. Thus, in this study, we aim to identify antiviral compounds against the Spike protein of Omicron, which binds to the human angiotensin-converting enzyme 2 (ACE2) receptor and facilitates virus invasion. Initially, docking-based virtual screening of the in-house database was performed to extract the potential hit compounds against the Spike protein. The obtained hits were optimized by DFT calculations to determine the electronic properties and molecular reactivity of the compounds. Further, MD simulation studies were carried out to evaluate the dynamics of protein-ligand interactions at an atomistic level in a time-dependent manner. Collectively, five compounds (AKS-01, AKS-02, AKS-03, AKS-04, and AKS-05) with diverse scaffolds were identified as potential hits against the Spike protein of Omicron. Our study paves the way for further in vitro and in vivo studies.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Antibodies, Monoclonal , Antibodies, Viral , Antiviral Agents/pharmacology , COVID-19/drug therapy , Cheminformatics , Humans , Ligands , Pandemics , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
4.
Virology ; 572: 28-43, 2022 07.
Article in English | MEDLINE | ID: covidwho-1991334

ABSTRACT

The newly discovered SARS-CoV-2 Omicron variant B.1.1.529 is a Variant of Concern (VOC) announced by the World Health Organization (WHO). It's becoming increasingly difficult to keep these variants from spreading over the planet. The fifth wave has begun in several countries because of Omicron variant, and it is posing a threat to human civilization. As a result, we need effective vaccination that can tackle Omicron SARS-CoV-2 variants that are bound to emerge. Therefore, the current study is an initiative to design a peptide-based chimeric vaccine that may potentially battle SARS-CoV-2 Omicron variant. As a result, the most relevant epitopes present in the mutagenic areas of Omicron spike protein were identified using a set of computational tools and immunoinformatic techniques to uncover common MHC-1, MHC-II, and B cell epitopes that may have the ability to influence the host immune mechanism. A final of three epitopes from CD8+ T-cell, CD4+ T-cell epitopes, and B-cell were shortlisted from spike protein, and that are highly antigenic, IFN-γ inducer, as well as overlapping for the construction of twelve vaccine models. As a result, the antigenic epitopes were coupled with a flexible and stable peptide linker, and the adjuvant was added at the N-terminal end to create a unique vaccine candidate. The structure of a 3D vaccine candidate was refined, and its quality was assessed by using web servers. However, the applied immunoinformatic study along with the molecular docking and simulation of 12 modeled vaccines constructs against six distinct HLAs, and TLRs (TLR2, and TLR4) complexes revealed that the V1 construct was non-allergenic, non-toxic, highly immunogenic, antigenic, and most stable. The vaccine candidate's stability was confirmed by molecular dynamics investigations. Finally, we studied the expression of the suggested vaccination using codon optimization and in-silico cloning. The current study proposed V1 Multi-Epitope Vaccine (MEV) as a significant vaccine candidate that may help the scientific community to treat SARS-CoV-2 infections.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevention & control , COVID-19 Vaccines/genetics , Computational Biology , Epitopes, B-Lymphocyte , Epitopes, T-Lymphocyte/genetics , Humans , Molecular Docking Simulation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Vaccines, Subunit/genetics
5.
J Infect Dev Ctries ; 16(6): 959-965, 2022 06 30.
Article in English | MEDLINE | ID: covidwho-1924346

ABSTRACT

INTRODUCTION: India witnessed the catastrophic second wave of COVID-19 during the summer months of 2021. Many patients with non-resolution of symptoms admitted to dedicated COVID-19 treatment centers required prolonged inpatient care which led to the unavailability of beds for other COVID-19 patients. The objective of this study was to determine the duration of SARS-CoV-2 positivity in moderate and severe COVID-19 patients requiring long-term pulmonary care as well as to find out the association between different variables with the persistence of the virus. METHODOLOGY: A retrospective chart review of clinical and laboratory data of patients with moderate and severe COVID-19 between 1st April 2021 and 15th July 2021 admitted for more than 28 days and requiring long-term pulmonary care was carried out at National Cancer Institute, AIIMS, India. SARS-CoV-2 RNA was detected with real-time reverse transcriptase-polymerase chain reaction-based tests. Data from all consecutively included patients satisfying the selection criteria were presented temporally and analyzed by Fisher's exact test (p < 0.05). RESULTS: All 51 patients tested positive for SARS-CoV-2 RNA at the 5th week of initial laboratory confirmation of COVID-19. The majority of the patients (38; 74.5%) remained positive for viral RNA till the 6th week and the median duration of viral positivity was 45 days. The clinical presentation of SARI at admission was significantly higher among patients with viral persistence till the 6th week (p < 0.05). CONCLUSIONS: The median duration of the viral positivity was 45 days and SARI at admission was significantly associated with viral persistence till the 6th week.


Subject(s)
COVID-19 , Pandemics , COVID-19/drug therapy , COVID-19/epidemiology , Humans , RNA, Viral , Retrospective Studies , SARS-CoV-2
6.
Frontiers in chemistry ; 10, 2022.
Article in English | EuropePMC | ID: covidwho-1897905

ABSTRACT

The pandemic of COVID-19, caused by SARS-CoV-2, has globally affected the human health and economy. Since the emergence of the novel coronavirus SARS-CoV-2, the life-threatening virus continues to mutate and evolve. Irrespective of acquired natural immunity and vaccine-induced immunity, the emerging multiple variants are growing exponentially, crossing the territorial barriers of the modern world. The rapid emergence of SARS-CoV-2 multiple variants challenges global researchers regarding the efficacy of available vaccines and variant transmissibility. SARS-CoV-2 surface-anchored S-protein recognizes and interacts with the host-cell ACE2, facilitating viral adherence and entrance into the cell. Understanding the interfacial interactions between the spike protein of SARS-CoV-2 variants and human ACE2 receptor is important for the design and development of antiviral therapeutics against SARS-CoV-2 emerging variants. Despite extensive research, the crucial determinants related to the molecular interactions between the spike protein of SARS-CoV-2 variants and host receptors are poorly understood. Thus, in this study, we explore the comparative interfacial binding pattern of SARS-CoV-2 spike RBD of wild type, Delta, and Omicron with the human ACE2 receptor to determine the crucial determinants at the atomistic level, using MD simulation and MM/GBSA energy calculations. Based on our findings, the substitution of Q493R, G496S, Q498R, and Y505H induced internal conformational changes in Omicron spike RBD, which leads to higher binding affinity than Delta spike RBD with the human ACE2 receptor, eventually contributing to higher transmission and infectivity. Taken together, these results could be used for the structure-based design of effective antiviral therapeutics against SARS-CoV-2 variants.

7.
Trop Med Infect Dis ; 7(5)2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1847405

ABSTRACT

The authors wish to revise the second citation of reference [26] to [27] in the original article main text [...].

8.
J Family Med Prim Care ; 11(1): 118-122, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1726355

ABSTRACT

Background: Asymptomatic carriers are responsible for the consistent spread of coronavirus disease 2019 (COVID-19) in the community. The Government of India has deputed house-to-house survey teams to aid in identifying asymptomatic individuals and their susceptible contacts. We selected door-to-door survey teams of a COVID-19 red zone in western India and determined their infectioncontrol practices and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobin G (IgG) status. Materials and Methods: This single-day prospective cross-sectional study was conducted by the Department of Microbiology of a tertiary care hospital of Jodhpur, in collaboration with the Rajasthan State Health Services. Participants were asked to fill out a questionnaire regarding personal protective equipment (PPE) use after written informed consent. Venous blood samples were collected and Kavach enzyme-linked immunosorbent assay (ELISA) (J Mitra and Co.) was performed to determine anti-SARS-CoV-2 IgG status. Results: Out of the total 39 participants, IgG antibody was detected in four. Of them, three reported mild symptoms in the past. Out of two previously real-time polymerase chain reaction (RT-PCR) SARS-CoV-2-positive participants, only one had detectable IgG antibodies (Ab) in serum. Cloth mask was used by 24, N95 mask by 11, and surgical masks by four. Conclusion: Anti-SARS-CoV-2 IgG Abs were detected among four members of house-to-house COVID-19 survey teams in Jodhpur. Most of the team members used cloth masks, whereas the Government of India guidelines has recommended triple-layered surgical masks as minimum essential PPE for healthcare workers in India. More such studies should be conducted to ascertain infection prevention and control practices among such vulnerable frontline workers in our country.

9.
Clin Infect Dis ; 74(10): 1776-1785, 2022 05 30.
Article in English | MEDLINE | ID: covidwho-1708084

ABSTRACT

BACKGROUND: Households are hot spots for severe acute respiratory syndrome coronavirus 2 transmission. METHODS: This prospective study enrolled 100 coronavirus disease 2019 (COVID-19) cases and 208 of their household members in North Carolina though October 2020, including 44% who identified as Hispanic or non-White. Households were enrolled a median of 6 days from symptom onset in the index case. Incident secondary cases within the household were detected using quantitative polymerase chain reaction of weekly nasal swabs (days 7, 14, 21) or by seroconversion at day 28. RESULTS: Excluding 73 household contacts who were PCR-positive at baseline, the secondary attack rate (SAR) among household contacts was 32% (33 of 103; 95% confidence interval [CI], 22%-44%). The majority of cases occurred by day 7, with later cases confirmed as household-acquired by viral sequencing. Infected persons in the same household had similar nasopharyngeal viral loads (intraclass correlation coefficient = 0.45; 95% CI, .23-.62). Households with secondary transmission had index cases with a median viral load that was 1.4 log10 higher than those without transmission (P = .03), as well as higher living density (more than 3 persons occupying fewer than 6 rooms; odds ratio, 3.3; 95% CI, 1.02-10.9). Minority households were more likely to experience high living density and had a higher risk of incident infection than did White households (SAR, 51% vs 19%; P = .01). CONCLUSIONS: Household crowding in the context of high-inoculum infections may amplify the spread of COVID-19, potentially contributing to disproportionate impact on communities of color.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Crowding , Family Characteristics , Humans , Prospective Studies , United States , Viral Load
10.
Journal of Contemporary Ethnography ; : 08912416211067563, 2022.
Article in English | Sage | ID: covidwho-1625350

ABSTRACT

Over the past year, COVID-19 and the restrictions imposed in its wake have meant that a range of research methodologies involving social contact could no longer be pursued. Whilst this time has been challenging, this article aims to showcase how it nonetheless presents opportunities for methodological innovation that can be carried forward into the future. Drawing upon an autoethnographic dissertation that sought to conceptualize the researcher?s lived experience in Scotland?s lockdown as an assemblage that was situated within, and intersected with, the wider ?lockdown cultural assemblage,? it proceeds chronologically from how the research began to inductively drawn findings on shifts to lived experience produced by the lockdown across five interrelated dimensions to lived experience: embodiment, spatiality, temporality, a changing vocabulary of sociality, and narratological environment and broader context. In recounting this journey, it demonstrates how assemblage theory can both benefit from, as well as transform, autoethnography as its primary methodological strategy.

11.
Trop Med Infect Dis ; 7(1)2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1625476

ABSTRACT

As the COVID-19 pandemic surged, lockdowns led to the cancellation of essential health services. As part of our Zero TB activities in Karachi, we adapted our approach to integrate activities for TB and COVID-19 to decrease the impact on diagnosis and linkage to care for TB treatment. We implemented the following: (1) integrated COVID-19 screening and testing within existing TB program activities, along with the use of an artificial intelligence (AI) software reader on digital chest X-rays; (2) home delivery of medication; (3) use of telehealth and mental health counseling; (4) provision of PPE; (5) burnout monitoring of health workers; and (6) patient safety and disinfectant protocol. We used programmatic data for six districts of Karachi from January 2018 to March 2021 to explore the time trends in case notifications, the impact of the COVID-19 pandemic, and service adaptations in the city. The case notifications in all six districts in Karachi were over 80% of the trend-adjusted expected notifications with three districts having over 90% of the expected case notifications. Overall, Karachi reached 90% of the expected case notifications during the COVID-19 pandemic. The collaborative efforts by the provincial TB program and private sector partners facilitated this reduced loss in case notifications.

12.
Am J Trop Med Hyg ; 106(1): 156-159, 2021 11 24.
Article in English | MEDLINE | ID: covidwho-1534405

ABSTRACT

Point-of-care (POC) tests to detect SARS-CoV-2 antibodies offer quick assessment of serostatus after natural infection or vaccination. We compared the field performance of the BioMedomics COVID-19 IgM/IgG Rapid Antibody Test against an ELISA in 303 participants enrolled in a SARS-CoV-2 household cohort study. The rapid antibody test was easily implemented with consistent interpretation across 14 users in a variety of field settings. Compared with ELISA, detection of seroconversion lagged by 5 to 10 days. However, it retained a sensitivity of 90% (160/177, 95% confidence interval [CI] 85-94%) and specificity of 100% (43/43, 95% CI 92-100%) for those tested 3 to 5 weeks after symptom onset. Sensitivity was diminished among those with asymptomatic infection (74% [14/19], 95% CI 49-91%) and early in infection (45% [29/64], 95% CI 33-58%). When used appropriately, rapid antibody tests offer a convenient way to detect symptomatic infections during convalescence.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Point-of-Care Testing , SARS-CoV-2/immunology , COVID-19/immunology , Cohort Studies , Enzyme-Linked Immunosorbent Assay/standards , Family Characteristics , Humans , Point-of-Care Testing/standards , SARS-CoV-2/isolation & purification
13.
Transbound Emerg Dis ; 68(6): 3126-3135, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1532919

ABSTRACT

The presence of foot-and-mouth disease virus (FMDV) of the O/ME-SA/Ind-2001e sublineage within Pakistan was initially detected in two samples collected during 2019. Analysis of further serotype O FMDVs responsible for disease outbreaks in 2019-2020 in the country has now identified the spread of this sublineage to 10 districts within two separate provinces in North-Eastern and North-Western Pakistan. Phylogenetic analysis indicates that these viruses are closely related to those circulating in Bhutan, Nepal and India. The VP1 coding sequences of these viruses from Pakistan belong to three distinct clusters, which may indicate multiple introductions of this virus sublineage, although the routes of introduction are unknown. Vaccine matching studies against O1 Manisa, O 3039 and O TUR/5/2009 support the suitability of existing vaccine strains to control current field outbreaks, but further studies are warranted to monitor the spread and evolution of the O/ME-SA/Ind-2001e sublineage in the region. (145 words).


Subject(s)
Foot-and-Mouth Disease Virus , Foot-and-Mouth Disease , Animals , Disease Outbreaks/veterinary , Foot-and-Mouth Disease/epidemiology , Foot-and-Mouth Disease Virus/genetics , Pakistan/epidemiology , Phylogeny , Serogroup
14.
Pharmaceutics ; 13(11)2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1512542

ABSTRACT

Ceftriaxone has been a part of therapeutic regime for combating some of the most aggressive bacterial infections in the last few decades. However, increasing bacterial resistance towards ceftriaxone and other third generation cephalosporin antibiotics has raised serious clinical concerns especially due to their misuse in the COVID-19 era. Advancement in nanotechnology has converted nano-therapeutic vision into a plausible reality with better targeting and reduced drug consumption. Thus, in the present study, gold nanoparticles (GNPs) were synthesized by using ceftriaxone antibiotic that acts as a reducing as well as capping agent. Ceftriaxone-loaded GNPs (CGNPs) were initially characterized by UV-visible spectroscopy, DLS, Zeta potential, Electron microscopy and FT-IR. However, a TEM micrograph showed a uniform size of 21 ± 1 nm for the synthesized CGNPs. Further, both (CGNPs) and pure ceftriaxone were examined for their efficacy against Escherichia coli, Staphylococcus aureus, Salmonella abony and Klebsiella pneumoniae. CGNPs showed MIC50 as 1.39, 1.6, 1.1 and 0.9 µg/mL against E. coli, S. aureus, S. abony and K. pneumoniae, respectively. Interestingly, CGNPs showed two times better efficacy when compared with pure ceftriaxone against the tested bacterial strains. Restoring the potential of unresponsive or less efficient ceftriaxone via gold nanoformulations is the most alluring concept of the whole study. Moreover, applicability of the findings from bench to bedside needs further validation.

15.
J Epidemiol Glob Health ; 11(2): 230-232, 2021 06.
Article in English | MEDLINE | ID: covidwho-1194572

ABSTRACT

BACKGROUND: On September 5, 2020, India reported the second highest COVID-19 cases globally. Given India's unique disease burden including both infectious and chronic diseases, there is a need to study the survival patterns of COVID-19. We aimed to describe the factors associated with COVID-19 deaths in the State of Tamil Nadu that has the highest COVID-19 case burden among the Indian states, and to compare deaths among COVID patients with and without comorbidities. METHODS: We analyzed the first 1000 COVID deaths (1 March to 26 June 2020) and 1000 recent deaths at the time of analysis (1-10 August 2020). We examined data on facility (public vs private), age, gender, duration of illness prior to and/or during hospitalizations, symptoms, comorbidities and cause of death. We used R statistical program to do the analysis. We compared deaths among patients with and without comorbidities using Wilcoxon rank sum test. p < 0.05 was considered significant. RESULTS: First, we found a shorter time interval from onset of symptoms to death in India than that was reported in the USA and China. Second, young adults without comorbidities had shorter survival from the time of onset of symptoms irrespective of their timing of hospitalization. Third, hypothyroidism is a COVID-19 associated co-morbidity. Longitudinal studies are needed to further assess the thyroid-COVID-19 link. CONCLUSION: As COVID-19 infection rates are accelerating rapidly in India, it is crucial to sensitize young adults while protecting the elderly and other vulnerable populations.


Subject(s)
COVID-19/mortality , Comorbidity , Adult , Female , Humans , India/epidemiology , Male , Middle Aged , SARS-CoV-2
16.
J Mol Struct ; 1231: 129953, 2021 May 05.
Article in English | MEDLINE | ID: covidwho-1036345

ABSTRACT

The pandemic of COVID-19 has an unprecedented impact on global health and economy. The novel SARS-CoV-2 is recognized as the etiological agent of current outbreak. Because of its contagious human-to-human transmission, it is an utmost global health emergency at present. To mitigate this threat many scientists and researchers are racing to develop antiviral therapy against the virus. Unfortunately, to date no vaccine or antiviral therapeutic is approved thus there is an urgent need to discover antiviral agent to help the individual who are at high risk. Virus main protease or chymotrypsin-like protease plays a pivotal role in virus replication and transcription; thus, it is considered as an attractive drug target to combat the COVID-19. In this study, multistep structure based virtual screening of CAS antiviral database is performed for the identification of potent and effective small molecule inhibitors against chymotrypsin-like protease of SARS-CoV-2. Consensus scoring strategy combine with flexible docking is used to extract potential hits. As a result of extensive virtual screening, 4 hits were shortlisted for MD simulation to study their stability and dynamic behavior. Insight binding modes demonstrated that the selected hits stabilized inside the binding pocket of the target protein and exhibit complementarity with the active site residues. Our study provides compounds for further in vitro and in vivo studies against SARS-CoV-2.

17.
J Nutr Biochem ; 90: 108571, 2021 04.
Article in English | MEDLINE | ID: covidwho-1001603

ABSTRACT

Vitamin D is customarily involved in maintaining bone and calcium homeostasis. However, contemporary studies have identified the implication of vitamin D in several cellular processes including cellular proliferation, differentiation, wound healing, repair and regulatory systems inclusive of host defence, immunity, and inflammation. Multiple studies have indicated corelations between low serum levels of vitamin D, perturbed pulmonary functions and enhanced incidences of inflammatory diseases. Almost all of the pulmonary diseases including acute lung injury, cystic fibrosis, asthma, COPD, Pneumonia and Tuberculosis, all are inflammatory in nature. Studies have displayed strong inter-relations with vitamin D deficiency and progression of lung disorders; however, the underlying mechanism is still unknown. Vitamin D has emerged to possess inhibiting effects on pulmonary inflammation while exaggerating innate immune defenses by strongly influencing functions of inflammatory cells including dendritic cells, monocyte/macrophages, T cells, and B cells along with structural epithelial cells. This review dissects the effects of vitamin D on the inflammatory cells and their therapeutic relevance in pulmonary diseases. Although, the data obtained is very limited and needs further corroboration but presents an exciting area of further research. This is because of its ease of supplementation and development of personalized medicine which could lead us to an effective adjunct and cost-effective method of therapeutic modality for highly fatal pulmonary diseases.


Subject(s)
Respiratory Tract Diseases/epidemiology , Vitamin D Deficiency/epidemiology , Vitamin D/blood , Acute Lung Injury/epidemiology , Animals , Asthma/epidemiology , Cystic Fibrosis/epidemiology , Humans , Incidence , Inflammation/epidemiology , Pneumonia/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Respiratory Tract Diseases/drug therapy , Tuberculosis/epidemiology , Vitamin D/administration & dosage , Vitamin D/metabolism , Vitamin D Deficiency/drug therapy
19.
J Mol Liq ; 324: 114706, 2021 Feb 15.
Article in English | MEDLINE | ID: covidwho-912505

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging health concern due to its high mortality rate of 35%. At present, no vaccine is available to protect against MERS-CoV infections. Therefore, an in silico search for potential antigenic epitopes in the non-redundant proteome of MERS-CoV was performed herein. First, a subtractive proteome-based approach was employed to look for the surface exposed and host non-homologous proteins. Following, immunoinformatics analysis was performed to predict antigenic B and T cell epitopes that were used in the design of a multi-epitopes peptide. Molecular docking study was carried out to predict vaccine construct affinity of binding to Toll-like receptor 3 (TLR3) and understand its binding conformation to extract ideas about its processing by the host immune system. We identified membrane protein, envelope small membrane protein, non-structural protein ORF3, non-structural protein ORF5, and spike glycoprotein as potential candidates for subunit vaccine designing. The designed multi-epitope peptide then linked to ß-defensin adjuvant is showing high antigenicity. Further, the sequence of the designed vaccine construct is optimized for maximum expression in the Escherichia coli expression system. A rich pattern of hydrogen and hydrophobic interactions of the construct was observed with the TLR3 allowing stable binding of the construct at the docked site as predicted by the molecular dynamics simulation and MM-PBSA binding energies. We expect that the panel of subunit vaccine candidates and the designed vaccine construct could be highly effective in immunizing populations from infections caused by MERS-CoV and could possible applied on the current pandemic COVID-19.

20.
Cureus ; 12(8): e9575, 2020 Aug 05.
Article in English | MEDLINE | ID: covidwho-723981

ABSTRACT

Background and objectives Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are rapidly spreading, posing a serious threat to the health of people worldwide, resulting in the World Health Organization officially declaring it a pandemic. There are several biochemical markers linked with predicting the severity of coronavirus disease. This study aims to identify the most effective predictive biomarker such as C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), procalcitonin (PCT), and D-dimer, among others, in predicting the clinical outcome of the disease. Materials and methods This study was conducted as a retrospective, observational, multi-centric study, including all admitted COVID-19 positive patients only. The disease outcome was followed along with the hospital course of every patient at the time of analysis. Baseline laboratory investigations of all patients were monitored both at admission and discharge. A comparative analysis was done between the survivors (n=263) and non-survivors (n=101). Statistical analysis was conducted using IBM SPSS Statistics for Windows Version 25 (Armonk, NY: IBM Corp.). Results Of 364 patients, 65.7% were in the isolation ward, and 34.3% were in the intensive care unit; 72.3% of patients survived, while 27.7% of patients died. The mean age of the study population was 52.6 ± 15.8 years with female patients significantly younger than male patients (p=0.001) and 50 to 75 years being the most common age group (p=0.121). Among the survivors versus non-survivors of COVID-19, there were significant differences in total leukocyte count (p<0.001), neutrophil count, (p<0.001), lymphocyte count (p<0.001), urea (p<0.001), serum bicarbonate (p=0.001), CRP levels (p<0.001), LDH (p=0.013), and D-dimer (p<0.001) at admission. At discharge, the laboratory values of non-surviving patients showed significant leukocytosis (p<0.001), neutrophilia (p<0.001), lymphocytopenia (p<0.001), decreased monocytes (p<0.001), elevated urea and creatinine (p<0.001), hypernatremia (p<0.001), decreased serum bicarbonate levels (p<0.001), elevated CRP level (p=0.040), LDH (p<0.001), ferritin (p=0.001), and D-dimer (p<0.001). Among the recovered patients, the laboratory investigations at admission were significantly different from those at discharge like increased platelets (p=0.007), lower neutrophil count (p=0.001), higher lymphocyte count (p=0.005), an improved creatinine (p=0.020), higher sodium (p=0.008), increased bicarbonate levels (p<0.001), decreased CRP levels (p<0.001), and a lower LDH (p=0.039). However, the laboratory values of non-surviving patients had shown a lower hemoglobin (p=0.016), increased mean cell volume (p<0.001), significantly increased total leukocyte count (p<0.001), increased urea and creatinine (p<0.001), hypernatremia (p<0.001), increased bicarbonate (p=0.025), elevated D-dimer levels (p=0.043), and elevated PCT (p=0.021) on discharge. Receiver operating characteristic analysis concluded LDH (area under the curve [AUC]: 0.875), D-dimer (AUC: 0.803), and PCT (AUC: 0.769) were superior biomarkers to ferritin (AUC: 0.714) and CRP (AUC: 0.711) in predicting the fatality of COVID-19. Conclusion Inflammatory markers are a useful guide for predicting mortality, and the study results concluded that LDH, PCT, D-dimer, CRP, and ferritin were effective biomarkers.

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