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1.
Aging Dis ; 13(3): 927-942, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1870133

ABSTRACT

Since September 2020, the SARS-CoV-2 variants have gained their dominance worldwide, especially in Kenya, Italy, France, the UK, Turkey, Indonesia, India, Finland, Ireland, Singapore, Denmark, Germany, and Portugal. In this study, we developed a model on the frequency of delta variants across 28 countries (R2= 0.1497), displaying the inheritance of mutations during the generation of the delta variants with 123,526 haplotypes. The country-wise haplotype network showed the distribution of haplotypes in USA (10,174), Denmark (5,637), India (4,089), Germany (2,350), Netherlands (1,899), Sweden (1,791), Italy (1,720), France (1,293), Ireland (1,257), Belgium (1,207), Singapore (1,193), Portugal (1,184) and Spain (1,133). Our analysis shows the highest haplotype in Europe with 84% and the lowest in Australia with 0.00001%. A model of scatter plot was generated with a regression line which provided the estimated rate of mutation, including 24.048 substitutions yearly. Our study concluded that the high global prevalence of the delta variants is due to a high frequency of infectivity, supporting the paradigm shift of the viral variants.

3.
EClinicalMedicine ; 46: 101359, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1828410

ABSTRACT

Background: There is an enormous knowledge gap on management strategies, clinical outcomes, and follow-up after kidney transplantation (KT) in recipients that have recovered from coronavirus disease (COVID-19). Methods: We conducted a multi-center, retrospective analysis in 23 Indian transplant centres between June 26, 2020 to December 1, 2021 on KT recipients who recovered after COVID-19 infections. We analyzed clinical and biopsy-confirmed acute rejection (AR) incidence and used cox-proportional modeling to estimate multivariate-adjusted hazard ratios (HR) for predictors of AR. We also performed competing risk analysis. Additional outcome measures included graft loss, all-cause mortality, waiting time from a positive real-time polymerase test (RT-PCR) to KT, laboratory parameters, and quality of life in follow-up. Findings: Among 372 KT which included 38(10·21%) ABO-incompatible, 12(3·22%) sensitized, 64(17·20%) coexisting donors with COVID-19 history and 20 (5·37%) recipients with residual radiographic abnormalities, the incidence of AR was 34 (9·1%) with 1(0·26%) death censored graft loss, and 4(1·07%) all-cause mortality over a median (interquartile range) follow-up of 241 (106-350) days. In our cox hazard proportional analysis, absence of oxygen requirement during COVID-19 compared to oxygen need [HR = 0·14(0·03-0·59); p-value = 0·0071], and use of thymoglobulin use compared to other induction strategies [HR = 0·17(0·03-0.95); p-value = 0·044] had a lower risk for AR. Degree of Human leukocyte antigen (HLA) DR mismatch had the highest risk of AR [HR = 10.2(1·74-65·83); p-value = 0·011]. With competing risk analysis, with death as a competing event, HLA DR mismatch, and oxygen requirement continued to be associated with AR. Age, gender, obesity, inflammatory markers, dialysis vintage, steroid use, sensitization and ABO-incompatibility have not been associated with a higher risk of AR. The median duration between COVID-19 real time polymerase test negativity to transplant was 88(40-145) days (overall), and ranged from 88(40-137), 65(42-120), 110(49-190), and 127(64-161) days in World Health Organization ordinal scale ≤ 3, 4, 5, and 6-7, respectively. There was no difference in quality of life, tacrolimus levels, blood counts, and mean serum creatinine assessed in patients with a past COVID-19 infection independent of severity. Interpretation: Our findings support that the outcomes of KT after COVID-19 recovery are excellent with absence of COVID-19 sequelae during follow-up. Additionally, there does not seem to be a need for changes in the induction/immunosuppression regimen based on the severity of COVID-19. Funding: Sanofi.

4.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1801589

ABSTRACT

Many novel drugs were used in COVID19 pandemic to improve outcome. One such molecule is Methylene blue which is a, tricyclic phenothiazine compound approved for the treatment of acquired methemoglobinemia and some other uses US FDA. This molecule was found to inhibit the interaction of COVID19 virus and target cells in dose dependent manner. It was also found to inhibit interaction of viron with host cells, by inhibiting interaction of SARS CoV2 spike protein and ACE inhibitor receptor interactions. MATERIAL AND METHODS: A) Aim & Objectives: To evaluate the effect of Nebulised Methylene blue on the clinical course and outcomes of patients with COVID-19 infections. B) Study design Observational Study C) Participants 63 COVID19 RT-PCR positive cases divided in 3 groups. Group 1 consists of patients who were prescribed Methylene blue nebulization in form of Methylene blue 0.5 mg via nebulization along with bronchodilator Levosalbutamol (1.25 mg) + Ipratropium (500 mcg) three times a day . Group 2 consists of patients with Methylene blue nebulization in form of Methylene blue 0.5 mg via nebulization along with inhalational steroid Budesonide (1 mg). Group 3 acted were those patients who had no Methylene blue nebulisation in their treatment. OBSERVATION: 1) Analysis 63 cases were divided in 3 groups of 21 each, descriptive and frequency analysis of cases in groups are shown. CONCLUSION: No statistically significant difference in outcome measures like Spo2, duration of hospital stay or inflammatory markers. A general trend of fall in inflammatory markers and O2 requirements in group receiving methylene blue but this difference was not consistantly statistically significant.


Subject(s)
COVID-19 , Methemoglobinemia , COVID-19/drug therapy , Humans , Methylene Blue/pharmacology , Methylene Blue/therapeutic use , Pandemics , SARS-CoV-2
5.
Indian J Med Microbiol ; 2022 Apr 20.
Article in English | MEDLINE | ID: covidwho-1796693

ABSTRACT

Cyclospora spp. is an important cause of traveler's diarrhea or water and food-borne diarrhoeal diseases. We present an interesting but rare case report of cyclosporiasis in a 51-year-old male who had undergone renal allograft transplant six years ago. He also had a past history of tuberculosis, cytomegalovirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and hepatitis C infection and was being treated with immunosuppressants. The patient had a prolonged history of gastrointestinal manifestations with recent acute onset of watery diarrhea associated with abdominal cramps. Stool examination after modified Ziehl-Neelsen staining revealed oocysts of Cyclospora spp. The patient was successfully treated with cotrimoxazole.

6.
Infect Genet Evol ; 101: 105282, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1783642

ABSTRACT

BACKGROUND: The massive increase in COVID-19 infection had generated a second wave in India during May-June 2021 with a critical pandemic situation. The Delta variant (B.1.617.2) was a significant factor during the second wave. Conversely, the UK had passed through the crucial phase of the pandemic from November to December 2020 due to B.1.1.7. The study tried to comprehend the pandemic response in the UK and India to the spread of the B.1.1.7 (Alpha, UK) variant and B.1.617.2 (Delta, India) variant. METHODS: This study was performed in three directions to understand the pandemic response of the two emerging variants. First, we served comparative genomics, such as genome sequence submission patterns, mutational landscapes, and structural landscapes of significant mutations (N501Y, D614G, L452R, E484Q, and P681R). Second, we performed evolutionary epidemiology using molecular phylogenetics, scatter plots of the cluster evaluation, country-wise transmission pattern, and frequency pattern. Third, the receptor binding pattern was analyzed using the Wuhan reference strain and the other two variants. RESULTS: The study analyzed the country-wise and region-wise genome sequences and their submission pattern, molecular phylogenetics, scatter plot of the cluster evaluation, country-wise geographical distribution and transmission pattern, frequency pattern, entropy diversity, and mutational landscape of the two variants. The structural pattern was analyzed in the N501Y, D614G L452R, E484Q, and P681R mutations. The study found increased molecular interactivity between hACE2-RBD binding of B.1.1.7 and B.1.617.2 compared to the Wuhan reference strain. Our receptor binding analysis showed a similar indication pattern for hACE2-RBD of these two variants. However, B.1.617.2 offers slightly better stability in the hACE2-RBD binding pattern through MD simulation than B.1.1.7. CONCLUSION: The increased hACE2-RBD binding pattern of B.1.1.7 and B.1.617.2 might help to increase the infectivity compared to the Wuhan reference strain.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , COVID-19/epidemiology , Genomics , Humans , Mutation , Pandemics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/metabolism , United Kingdom/epidemiology
7.
Int Immunopharmacol ; 108: 108766, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1778220

ABSTRACT

Hybrid immunity has been accepted as the most robust immunity to fight against SARS-CoV-2. The hybrid immunity against the virus is produced in individuals who have contracted the disease and received the COVID-19 vaccine. This happens due to the cumulative effect of natural and acquired (vaccine) immunity, which provides higher antibody responses compared to natural and vaccine-produced immunity alone. Scientists have noted that it provides about 25 to 100 times higher antibody responses than natural and vaccine-produced immunity alone. Here, we have tried to illustrate the molecular basis of hybrid immunity against various SARS-CoV-2 variants. We have described hybrid immunity under different headings, which are as follows: an overview of hybrid immunity; a comparison between herd immunity and hybrid immunity against SARS-CoV-2; hybrid immunity in different countries; hybrid immunity and different SARS-CoV-2 variants; the molecular basis of hybrid immunity; and hybrid immunity in Indian scenario. India's large population has recovered from SARS-CoV-2, and data shows that over 1000 million of the population received at least one dose of the vaccine. Besides, many infected individuals who have recovered also received at least one dose of the vaccine leading to hybrid immunity with a less severe third wave compared to the first and second waves. Based on the available data, we hypothesize that people's hybrid immunity could be a major cause of the less severe third wave.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19 Vaccines , Humans , SARS-CoV-2
8.
Journal of Media Ethics ; : 1-3, 2022.
Article in English | Academic Search Complete | ID: covidwho-1758589
9.
Appl Microbiol Biotechnol ; 105(24): 9035-9045, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1748501

ABSTRACT

The progression of the COVID-19 pandemic has generated numerous emerging variants of SARS-CoV-2 on a global scale. These variants have gained evolutionary advantages, comprising high virulence and serious infectivity due to multiple spike glycoprotein mutations. As a reason, variants are demonstrating significant abilities to escape the immune responses of the host. The D614G mutation in the S-glycoprotein of SARS-CoV-2 variants has shown the most efficient interaction with the ACE2 receptor of the cells. This explicit mutation at amino acid position 614 (aspartic acid-to-glycine substitution) is the prime cause of infection and re-infection. It changes the conformation of RBD and cleavage patterns S-glycoprotein with higher stability, replication fitness, and fusion efficiencies. Therefore, this review aims to provide several crucial pieces of information associated with the D614 mutational occurrence of SARS-CoV-2 variants and their infectivity patterns. This review will also effectively emphasize the mechanism of action of D614G mutant variants, immune escape, and partial vaccine escape of this virus. Furthermore, the viral characteristic changes leading to the current global pandemic condition have been highlighted. Here, we have tried to illustrate a novel direction for future researchers to develop effective therapeutic approaches and counterweight strategies to minimize the spread of COVID-19.Key points• D614G mutation arises within the S-glycoprotein of significant SARS-CoV-2 variants.• The D614G mutation affects infection, re-infection, cleavage patterns of S-glycoprotein, and replication fitness of SARS-CoV-2 variants.• The D614G mutation influences the immunity and partial vaccine escape.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Mutation , Pandemics , Spike Glycoprotein, Coronavirus/genetics
10.
PLoS One ; 17(3): e0263916, 2022.
Article in English | MEDLINE | ID: covidwho-1742004

ABSTRACT

OBJECTIVES: Ground-glass opacity (GGO)-a hazy, gray appearing density on computed tomography (CT) of lungs-is one of the hallmark features of SARS-CoV-2 in COVID-19 patients. This AI-driven study is focused on segmentation, morphology, and distribution patterns of GGOs. METHOD: We use an AI-driven unsupervised machine learning approach called PointNet++ to detect and quantify GGOs in CT scans of COVID-19 patients and to assess the severity of the disease. We have conducted our study on the "MosMedData", which contains CT lung scans of 1110 patients with or without COVID-19 infections. We quantify the morphologies of GGOs using Minkowski tensors and compute the abnormality score of individual regions of segmented lung and GGOs. RESULTS: PointNet++ detects GGOs with the highest evaluation accuracy (98%), average class accuracy (95%), and intersection over union (92%) using only a fraction of 3D data. On average, the shapes of GGOs in the COVID-19 datasets deviate from sphericity by 15% and anisotropies in GGOs are dominated by dipole and hexapole components. These anisotropies may help to quantitatively delineate GGOs of COVID-19 from other lung diseases. CONCLUSION: The PointNet++ and the Minkowski tensor based morphological approach together with abnormality analysis will provide radiologists and clinicians with a valuable set of tools when interpreting CT lung scans of COVID-19 patients. Implementation would be particularly useful in countries severely devastated by COVID-19 such as India, where the number of cases has outstripped available resources creating delays or even breakdowns in patient care. This AI-driven approach synthesizes both the unique GGO distribution pattern and severity of the disease to allow for more efficient diagnosis, triaging and conservation of limited resources.


Subject(s)
COVID-19/diagnostic imaging , Lung/pathology , Radiographic Image Interpretation, Computer-Assisted/methods , Artificial Intelligence , COVID-19/pathology , Female , Humans , India , Lung/diagnostic imaging , Male , Patient Acuity , Retrospective Studies , Tomography, X-Ray Computed/methods , Unsupervised Machine Learning
11.
Geroscience ; 44(2): 619-637, 2022 04.
Article in English | MEDLINE | ID: covidwho-1729366

ABSTRACT

The Omicron variant has been detected in nearly 150 countries. We analyzed the mutational landscape of Omicron throughout the genome, focusing the S-glycoprotein. We also evaluated mutations in the antibody-binding regions and observed some important mutations overlapping those of previous variants including N501Y, D614G, H655Y, N679K, and P681H. Various new receptor-binding domain mutations were detected, including Q493K, G496S, Q498R, S477N, G466S, N440K, and Y505H. New mutations were found in the NTD (Δ143-145, A67V, T95I, L212I, and Δ211) including one new mutation in fusion peptide (D796Y). There are several mutations in the antibody-binding region including K417N, E484A, Q493K, Q498R, N501Y, and Y505H and several near the antibody-binding region (S477N, T478K, G496S, G446S, and N440K). The impact of mutations in regions important for the affinity between spike proteins and neutralizing antibodies was evaluated. Furthermore, we examined the effect of significant antibody-binding mutations (K417N, T478K, E484A, and N501Y) on antibody affinity, stability to ACE2 interaction, and possibility of amino acid substitution. All the four mutations destabilize the antibody-binding affinity. This study reveals future directions for developing neutralizing antibodies against the Omicron variant.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Antibodies, Neutralizing/genetics , COVID-19/genetics , Glycoproteins/genetics , Humans , Mutation/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
12.
Transl Res ; 241: 83-95, 2022 03.
Article in English | MEDLINE | ID: covidwho-1720996

ABSTRACT

Patients with cancers have been severely affected by the COVID-19 pandemic. This is highlighted by the adverse outcomes in cancer patients with COVID-19 as well as by the impact of the COVID-19 pandemic on cancer care. Patients with cancer constitute a heterogeneous population that exhibits distinct mechanisms of immune dysfunction, associated with distinct systemic features of hot (T-cell-inflamed/infiltrated) and cold (Non-T-cell-inflamed and/or infiltrated) tumors. The former show hyper immune activated cells and a highly inflammatory environment while, contrastingly, the latter show the profile of a senescent and/or quiescent immune system. Thus, the evolution of SARS-CoV-2 infection in different types of cancers can show distinct trajectories which could lead to a variety of clinical and pathophysiological outcomes. The altered immunological environment including cytokines that characterizes hot and cold tumors will lead to different mechanisms of immune dysfunction, which will result in downstream effects on the course of SARS-CoV-2 infection. This review will focus on defining the known contributions of soluble pro- and anti-inflammatory mediators on immune function including altered T-cells and B-cells responses and as well on how these factors modulate the expression of SARS-CoV-2 receptor ACE2, TMPRSS2 expression, and lymph node fibrosis in cancer patients. We will propose immune mechanisms that underlie the distinct courses of SARS-CoV-2 infection in cancer patients and impact on the success of immune based therapies that have significantly improved cancer outcomes. Better understanding of the immune mechanisms prevalent in cancer patients that are associated to the outcomes of SARS-CoV-2 infection will help to identify the high-risk cancer patients and develop immune-based approaches to prevent significant adverse outcomes by targeting these pathways.


Subject(s)
COVID-19/complications , Neoplasms/immunology , COVID-19/immunology , COVID-19/virology , Humans , Outcome Assessment, Health Care , SARS-CoV-2/isolation & purification
13.
Transplantation ; 105(7): 1423-1432, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1704612

ABSTRACT

BACKGROUND: There is limited current knowledge on feasibility and safety of kidney transplantation in coronavirus disease-19 (COVID-19) survivors. METHODS: We present a retrospective cohort study of 75 kidney transplants in patients who recovered from polymerase chain reaction (PCR)-confirmed COVID-19 performed across 22 transplant centers in India from July 3, 2020, to January 31, 2021. We detail demographics, clinical manifestations, immunosuppression regimen, laboratory findings, treatment, and outcomes. Patients with a previous diagnosis of COVID-19 were accepted after documenting 2 negative severe acute respiratory syndrome coronavirus 2 PCR tests, normal chest imaging with complete resolution of symptom for at least 28 d and significant social distancing for 14 d before surgery. RESULTS: Clinical severity in patients ranged from asymptomatic (n = 17, 22.7%), mild (n = 36.48%), moderate (n = 15.20%), and severe (n = 7.9.3%) disease. Median duration between PCR positive to transplant was 60 d (overall) and increased significantly from asymptomatic, mild, moderate, and severe disease (49, 57, 83, 94 d, P 0.019), respectively. All recipients and donors were asymptomatic with normal creatinine after surgery at a median (interquartile range) follow-up of 81 (56-117) d without any complications relating to surgery or COVID-19. Patient and graft survival was 100%, and acute rejection was reported in 6.6%. CONCLUSIONS: Prospective kidney transplant recipients post-COVID-19 can be considered for transplantation after comprehensive donor and recipient screening before surgery using a combination of clinical, radiologic, and laboratory criteria, careful pretransplant evaluation, and individualized risk-benefit analysis. Further large-scale prospective studies with longer follow-up will better clarify our initial findings. To date, this remains the first and the largest study of kidney transplantation in COVID-19 survivors.


Subject(s)
COVID-19/complications , Kidney Failure, Chronic/surgery , Kidney Transplantation , Adult , Aged , COVID-19/diagnosis , Donor Selection/methods , Female , Follow-Up Studies , Humans , India , Kidney Failure, Chronic/complications , Male , Middle Aged , Patient Selection , Retrospective Studies , Survivors , Treatment Outcome
14.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1696199

ABSTRACT

The infective SARS-CoV-2 is more prone to immune escape. Presently, the significant variants of SARS-CoV-2 are emerging in due course of time with substantial mutations, having the immune escape property. Simultaneously, the vaccination drive against this virus is in progress worldwide. However, vaccine evasion has been noted by some of the newly emerging variants. Our review provides an overview of the emerging variants’ immune escape and vaccine escape ability. We have illustrated a broad view related to viral evolution, variants, and immune escape ability. Subsequently, different immune escape approaches of SARS-CoV-2 have been discussed. Different innate immune escape strategies adopted by the SARS-CoV-2 has been discussed like, IFN-I production dysregulation, cytokines related immune escape, immune escape associated with dendritic cell function and macrophages, natural killer cells and neutrophils related immune escape, PRRs associated immune evasion, and NLRP3 inflammasome associated immune evasion. Simultaneously we have discussed the significant mutations related to emerging variants and immune escape, such as mutations in the RBD region (N439K, L452R, E484K, N501Y, K444R) and other parts (D614G, P681R) of the S-glycoprotein. Mutations in other locations such as NSP1, NSP3, NSP6, ORF3, and ORF8 have also been discussed. Finally, we have illustrated the emerging variants’ partial vaccine (BioNTech/Pfizer mRNA/Oxford-AstraZeneca/BBIBP-CorV/ZF2001/Moderna mRNA/Johnson & Johnson vaccine) escape ability. This review will help gain in-depth knowledge related to immune escape, antibody escape, and partial vaccine escape ability of the virus and assist in controlling the current pandemic and prepare for the next.

15.
Aging Dis ; 12(8): 2173-2195, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1667753

ABSTRACT

Newly emerging significant SARS-CoV-2 variants such as B.1.1.7, B.1.351, and B.1.1.28 are the variant of concern (VOC) for the human race. These variants are getting challenging to contain from spreading worldwide. Because of these variants, the second wave has started in various countries and is threatening human civilization. Thus, we require efficient vaccines that can combat all emerging variants of SARS-CoV-2. Therefore, we took the initiative to develop a peptide-based next-generation vaccine using four variants (Wuhan variant, B.1.1.7, B.1.351, and B.1.1.28) that could potentially combat SARS-CoV-2 variants. We applied a series of computational tools, servers, and software to identify the most significant epitopes present on the mutagenic regions of SARS-CoV-2 variants. The immunoinformatics approaches were used to identify common B cell derived T cell epitopes, influencing the host immune system. Consequently, to develop a novel vaccine candidate, the antigenic epitopes were linked with a flexible and stable peptide linker, and the adjuvant was added at the N-terminal end. 3D vaccine candidate structure was refined, and quality was assessed using web servers. The physicochemical properties and safety parameters of the vaccine construct were assessed through bioinformatics and immunoinformatics tools. The molecular docking analysis between TLR4/MD2 and the proposed vaccine candidate demonstrated a satisfactory interaction. The molecular dynamics studies confirmed the stability of the vaccine candidate. Finally, we optimized the proposed vaccine through codon optimization and in silico cloning to study the expression. Our multi-epitopic next-generation peptide vaccine construct can boost immunity against the Wuhan variant and all significant mutant variants of SARS-CoV-2.

16.
Journal of Hazardous Materials Advances ; : 100050, 2022.
Article in English | ScienceDirect | ID: covidwho-1664950

ABSTRACT

Young children are a vulnerable population cohort. They receive higher exposure to particulate matter than adults in outdoor roadside environments, necessitating research on an unexplored area of exposure to young children in electric bike trailers. We simulated the exposure profiles of an adult cyclist and young children sitting in a bike-trailer attached to it for multiple air pollutants – particulate matter ≤10µm in aerodynamic diameter (PM10), ≤2.5µm (PM2.5;fine particles), ≤1µm (PM1), BC, and CO2 – during the school run in the morning and afternoon hours. We assessed the differences in their exposure concentrations and analysed the impact of trailer covers and COVID-19 lockdown restrictions via simultaneous measurements under six settings forming three scenarios: (i) bike-trailer versus adult cyclist height;(ii) bike-trailer with and without the cover;and (iii) exposure during the lockdown and eased-lockdown periods. We carried out a total of 82 single runs covering a length of 176 km. These runs were repeated on a 2.1 km long predefined route between an origin (University campus) and destination (a local school) to simulate morning drop-off (08:00-10:00h;local time) and afternoon pick-up (15:00-17:00h) times of school children. Substantial variability was observed in concentrations of measured pollutants within each run (e.g., up to 97% for BC) and between different runs (e.g., ∼93% for PM2.5 during morning versus afternoon) in bike-trailer. Compared with cyclist height, the average bike-trailer concentration of fine and coarse particles was higher by up to 14% and 18%, respectively, during both morning and afternoon runs. The lockdown restrictions when schools were closed led to a reduction in bike-trailer PM2.5 concentrations by up to 91% compared with eased lockdown period when schools re-opened in March 2021. Trailer covers led up to 50% (fine particles) and 24% (BC;a component of PM2.5) reductions in concentrations compared with trailers without cover. Young children carried in bike trailers are exposed to higher air pollution concentrations compared with the cyclist, particularly during peak morning periods at urban pollution hotspots such as traffic lights.

17.
Am J Trop Med Hyg ; 105(6): 1472-1475, 2021 Oct 04.
Article in English | MEDLINE | ID: covidwho-1629955

ABSTRACT

Human lives and nations' economies have been adversely affected worldwide by the COVID-19 pandemic. The hyperinflammatory state associated with the disease may be related to mortality. Systemic glucocorticoid is the first-line therapy for cytokine storm. Various immunomodulatory drugs such as tocilizumab and baricitinib have been used in those not responding to glucocorticoid monotherapy. Amid the peak crisis of COVID-19 in India, there was an extreme paucity of medications, oxygen, and hospital beds. We describe three patients with COVID-19 who received low-dose tofacitinib (an oral Janus kinase inhibitor) in addition to moderate-dose glucocorticoid. These patients were treated at their homes, as the hospitals were short of beds. Rapid reduction in hypoxemia along with gradual resolution of other signs of the disease were observed. The results are reassuring regarding the feasibility of managing of severe COVID-19 outside the hospital setting when healthcare resources are overwhelmed by pandemic-related caseload.


Subject(s)
COVID-19/drug therapy , Piperidines/therapeutic use , Pyrimidines/therapeutic use , SARS-CoV-2 , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Cytokine Release Syndrome/prevention & control , Cytokines/genetics , Cytokines/metabolism , Enoxaparin/administration & dosage , Enoxaparin/therapeutic use , Female , Gene Expression Regulation/drug effects , Humans , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Middle Aged , Piperidines/administration & dosage , Prednisone/administration & dosage , Prednisone/therapeutic use , Pyrimidines/administration & dosage
18.
Mol Biotechnol ; 64(5): 510-525, 2022 May.
Article in English | MEDLINE | ID: covidwho-1603883

ABSTRACT

Presently, the world needs safe and effective vaccines to overcome the COVID-19 pandemic. Our work has focused on formulating two types of mRNA vaccines that differ in capacity to copy themselves inside the cell. These are non-amplifying mRNA (NRM) and self-amplifying mRNA (SAM) vaccines. Both the vaccine candidates encode an engineered viral replicon which can provoke an immune response. Hence we predicted and screened twelve epitopes from the spike glycoprotein of SARS-CoV-2. We used five CTL, four HTL, and three B-cell-activating epitopes to formulate each mRNA vaccine. Molecular docking revealed that these epitopes could combine with HLA molecules that are important for boosting immunogenicity. The B-cell epitopes were adjoined with GPGPG linkers, while CTL and HTL epitopes were linked with KK linkers. The entire protein chain was reverse translated to develop a specific NRM-based vaccine. We incorporate gene encoding replicase in the upstream region of CDS encoding antigen to design the SAM vaccine. Subsequently, signal sequences were added to human mRNA to formulate vaccines. Both vaccine formulations translated to produce the epitopes in host cells, initiate a protective immune cascade, and generate immunogenic memory, which can counter future SARS-CoV-2 viral exposures before the onset of infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Bioengineering , COVID-19/prevention & control , COVID-19 Vaccines/genetics , Epitopes, B-Lymphocyte/genetics , Epitopes, T-Lymphocyte/genetics , Humans , Immunogenicity, Vaccine , Molecular Docking Simulation , Pandemics/prevention & control , RNA, Messenger/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccines, Synthetic
19.
Front Immunol ; 12: 724936, 2021.
Article in English | MEDLINE | ID: covidwho-1592205

ABSTRACT

The COVID-19 pandemic has created an urgent situation throughout the globe. Therefore, it is necessary to identify the differentially expressed genes (DEGs) in COVID-19 patients to understand disease pathogenesis and the genetic factor(s) responsible for inter-individual variability. The DEGs will help understand the disease's potential underlying molecular mechanisms and genetic characteristics, including the regulatory genes associated with immune response elements and protective immunity. This study aimed to determine the DEGs in mild and severe COVID-19 patients versus healthy controls. The Agilent-085982 Arraystar human lncRNA V5 microarray GEO dataset (GSE164805 dataset) was used for this study. We used statistical tools to identify the DEGs. Our 15 human samples dataset was divided into three groups: mild, severe COVID-19 patients and healthy control volunteers. We compared our result with three other published gene expression studies of COVID-19 patients. Along with significant DEGs, we developed an interactome map, a protein-protein interaction (PPI) pattern, a cluster analysis of the PPI network, and pathway enrichment analysis. We also performed the same analyses with the top-ranked genes from the three other COVID-19 gene expression studies. We also identified differentially expressed lncRNA genes and constructed protein-coding DEG-lncRNA co-expression networks. We attempted to identify the regulatory genes related to immune response elements and protective immunity. We prioritized the most significant 29 protein-coding DEGs. Our analyses showed that several DEGs were involved in forming interactome maps, PPI networks, and cluster formation, similar to the results obtained using data from the protein-coding genes from other investigations. Interestingly we found six lncRNAs (TALAM1, DLEU2, and UICLM CASC18, SNHG20, and GNAS) involved in the protein-coding DEG-lncRNA network; which might be served as potential biomarkers for COVID-19 patients. We also identified three regulatory genes from our study and 44 regulatory genes from the other investigations related to immune response elements and protective immunity. We were able to map the regulatory genes associated with immune elements and identify the virogenomic responses involved in protective immunity against SARS-CoV-2 infection during COVID-19 development.


Subject(s)
COVID-19/genetics , Gene Expression Profiling/methods , Gene Expression Regulation , Immunity/genetics , Aged , COVID-19/epidemiology , COVID-19/immunology , Female , Gene Ontology , Gene Regulatory Networks , Humans , Male , Middle Aged , Pandemics/prevention & control , Protein Interaction Maps/genetics , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Signal Transduction/genetics , Signal Transduction/immunology
20.
Indian J Nephrol ; 31(6): 531-535, 2021.
Article in English | MEDLINE | ID: covidwho-1574405

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. The pre-immunosuppressed state along with other existing co-morbidities can influence the outcomes of COVID-19 in transplant patients. MATERIAL AND METHODS: This was a single centre prospective cohort study done in kidney transplant recipients (KTRs), who underwent kidney transplantation (from December 2012 to November 2020), who were actively followed up at our centre and were diagnosed with COVID-19 disease between 1 April and 30 November 2020. RESULTS: A total of 62 kidney-transplant recipients tested positive for COVID-19. Their median age was 39 (19-61). Males were predominantly infected (87.1%). Fever was the most common symptom (77.42%). Thirteen (20.9%) had mild form of disease, 32 (51.6%) had moderate form and 17 (27.4%) had severe disease. Based on initial symptom, 18 (29.03%) were given home treatment, 29 (46.7%) were treated in isolation wards and 15 (24.1%) were treated in intensive care unit. Decrease in the dose of immunosuppressant (anti-metabolites in 67.7%, calcineurin inhibitor in 22.5%) was predominantly carried out as the initial mode of treatment. Remdesivir in 64.5% and anticoagulant therapy in 54.84% were given as a modality of treatment. Mortality rate in our study was 14.5%. CONCLUSIONS: Patients of kidney transplant are at high risk of getting infected with COVID-19, due to their immunosuppressed state. Initial symptoms in KTRs with COVID-19 are similar to that of the general population. Mortality rate is comparatively higher in KTRs as compared to general population.

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