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Background: Dialysis patients have a higher COVID-19 fatality rate than the general population and are priority candidates for SARS-CoV-2 vaccination. However, dialysis patients are immunocompromised, suggesting that they may develop a less immune response to COVID-19 vaccination than healthy individuals. Objective and Methods: A total of 358 hemodialysis patients who were twicevaccinated with BNT162b2 were included. SARS-CoV-2 IgG antibody titer was measured within 7 days to 1 month, 1∼2 months, and 3∼4 months after the second vaccination, and factors influencing antibody titer were statistically investigated. SARS-CoV-2 IgG measurement was performed using SARS-CoV-2 IgG II Quant Reagent (Abbott), which is a reagent to quantitatively measure IgG antibodies against the receptor-binding domain of SARS-CoV-2 spike protein. Results: The patients were 240 males (67%) and 118 females, ranging from 37 to 95 years old, with a median age of 70 years. Causes of kidney failure were diabetes mellitus in 35.2%, hypertensive kidney disease in 7.3%, glomerular disease in 30.5%, and polycystic kidney disease in 4.5% of the patients. Comorbidities were hypertension in 64.3% and diabetes in 48.9%. Steroids or immunosuppressive drugs were used in 9% of the patients. SARS-CoV-2 IgG antibody titers at 7 days to 1 month, 1 to 2 months, and 3 to 4 months (median 10, 42, and 98 days) after the second vaccination have the median of 4092 AU/mL(with interquartile range: 1354, 7592), 2199 (927, 4692), and 789 (323, 1559), respectively. Post-vaccination SARS-CoV-2 IgG titers were significantly correlated with Kt/V, the presence of autoimmune diseases, the use of steroids or immunosuppressive drugs, malignancy treatment, and serum albumin and hemoglobin levels. Multivariate analysis showed that the factors that decreased post-vaccination SARS-CoV-2 IgG titer were the use of steroids and immunosuppressive drugs, the presence of malignant tumors under treatment, and hypoalbuminemia. Conclusion: Compared to healthy subjects in previous reports, dialysis patients had lower SARS-CoV-2 IgG titers after COVID-19 vaccination, suggesting that the vaccine may not be sufficiently effective. In addition, SARS-CoV-2 IgG titers are likely to be even lower in patients at high risk for decreased immune response due to medications or comorbidities. Additional vaccination may be essential for hemodialysis patients who are expected to have low SARS-CoV-2 IgG titers.
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Background: Data are limited regarding the safety of and antibody response to the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid vaccine in adolescents and young adults with underlying disease. Methods: This prospective observational study enrolled patients age 12–25 years with chronic underlying disease who received 2 doses of BNT162b2. A 18-item questionnaire was used to assess adverse events within 7 days post-vaccination, and data regarding severe adverse events were collected from electronic medical records. An antibody titer for the receptor-binding domain of the spike protein in SARS-CoV-2 was used to assess antibody response after the second vaccine dose. Results: Study participants were 429 patients (241 [56.2%] age 12–15 years;188 [43.8%] age 16–25 years). The most common underlying diseases were genetic or chromosomal abnormalities and/or congenital anomalies, followed by endocrine or metabolic diseases;32% of participants were immunocompromised. Severe adverse events were observed after the second dose in 1 (0.4%) patient age 12–15 years and in 2 (1.1%) patients age 16–25 years;all patients recovered. Seropositivity after the second vaccine dose was 99.0%. The geometric mean antibody titer was higher in patients age 12–15 years versus 16–25 years (1603.3 [1321.8–1944.7] U/mL vs. 949.4 [744.2–1211.0] U/mL). Compared with immunocompetent patients, immunocompromised patients had a lower antibody titer (2106.8 [1917.5–2314.7] U/mL vs. 467.9 [324.4–674.8] U/mL). Conclusions: Vaccination with BNT162b2 was acceptably safe and immunogenic for adolescents and young adults with underlying disease. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases
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Objective: COVID19 is associated with vascular inflammation. IFN-alpha (IFNa) and IFN-lambda3 (IFNl3) are potent cytokines produced in viral infections. Their effects involve interferon-stimulated genes (ISGs) and may influence expression of angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) of SARS-CoV-2. We hypothesized that S1P-induced immune/inflammatory responses in endothelial cells (EC) are mediated via IFN-activated pathways Design and methods: Human ECs were stimulated with S1P (1 mg/mL), IFNa (100ng/mL) or IFNl3 (100IU/mL). Because ACE2, ADAM17 and TMPRSS2 are important for SARS-CoV-2 infection, we used inhibitors of ADAM17 (marimastat, 3.8 nM), ACE2 (MLN4760, 440pM), and TMPRSS2 (camostat, 50 mM). Gene and protein expression was investigated by real-time PCR and immunoblotting, respectively. Vascular function was assessed in mesenteric arteries from wild-type (WT) normotensive and hypertensive (LinA3) mice and in ISG15-deficient (ISG15KO) mice. Results: S1P increased expression of IFNa (3-fold), IFNl3 (4-fold) and ISGs (2-fold) in EC (p < 0.05). EC responses to IFNa (ISG15: 16-fold) were greater than to IFNl3 (ISG15: 1.7-fold) (p < 0.05). S1P increased gene expression of IL-6 (1.3-fold), TNFa (6.2-fold) and IL-1b (3.3-fold), effects that were amplified by IFNs. Only the ADAM17 inhibitor marimastat inhibited S1P effects. IFNa and IFNl3 increase protein expression of ADAM17 (27%) and TMPRSS2 (38%). No changes were observed on ACE2 expression. This was associated with increased phosphorylation of Stat1 (134%), Stat2 (102%), ERK1/2 (42%). EC production of IL-6 was increased by IFNa (1,230pg/mL) and IFNl3 (1,124pg/mL) vs control (591pg/mL). Nitric oxide generation and eNOS phosphorylation (Ser1177) were reduced by IFNa (40%) and IFNl3 (40%). Vascular functional responses demonstrated that endothelium-dependent vasorelaxation (% Emax) in vessels from WT-mice stimulated with IFNa (67%) and IFNl3 (71%) were reduced vs control (82%) (p < 0.05). Responses were not altered in vessels from ISG15KO mice. Increased contraction was observed only in vessels from hypertensive mice treated with IFNa (9.1 ± 0.5mN vs control: 7.3 ± 0.3mN) (p < 0.05). Conclusions: In ECs, S1P, IFNa and IFNl3 increased ISG15 and IL-6 by mechanisms dependent on ADAM17. IFNs amplifies endothelial cell inflammatory responses and induced vascular dysfunction through ISG15-dependent mechanisms, with augmented effects in hypertension. Our findings demonstrate that S1P induces immune/inflammatory responses that may be important in endotheliitis associated with COVID-19. This may be especially important in the presence of cardiovascular risk factors, including hypertension.
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The main aim of this study is to determine the bioactive compounds which have drug-like properties and has the potential to combat the spike-glycoprotein of SARS-CoV-2. The 6LXT protein of covid-19 was chosen from the protein data bank as a target protein. The compounds which are potentially capable to bind with the target were picked from the PubChem database and docked using the tool Autodock 4.2. Molecular docking of the molecules was done with the best conformations of the ligands and grid size was selected according to the hit compounds' interaction with the target protein. The ligand binding sites with the target molecules were predicted using MetaPocket 2.0. The docking Score of 50 compounds wascarried out and also toxicity studies were carried out. The compounds selected were calculated to identify the best conformations having drug-likeness properties. The top 10 compounds were chosen for the structure-activity relationship based on their binding interactions with the protein and ligand. The ligands then underwent the pharmacokinetic analysis followed by Lipinski's and all the results were finalized and categorized. ManzamineA, Imatinib, and basotinib were elected as the peak compounds with the binding energy -9.01kcal/mol, -8.71kcal/mol, and -8.01kcal/mol.
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Background/Aims: Several studies showed that patients with liver cirrhosis have an immune dysregulation leading to poor immunological response to vaccination. However, in literature there are few data about the response to SARS-CoV-2 vaccination in patients with chronic liver disease (CLD). Aims of the study are (is) the evaluation of safety and immunogenicity of booster dose in patients with CLD. Methods: From September 2021 to April 2022, all consecutive outpatients with CLD who completed the primary vaccination course and the booster dose for anti-SARS-CoV-2 vaccination were enrolled. Blood samples were collected 12-16 weeks after second dose and after booster dose. Collected samples were analyzed for detecting anti-Spike protein IgG using LIAISON TrimericS IgG chemiluminescent assay (Diasorin, Italy). Results: We enrolled 340 patients (187 Males, mean age:64.32±17.34years). Stratified by the presence of cirrhosis, 249 had CLD and 91 were cirrhotic whose 57 (62.24%) had portal hypertension. At the end of the primary vaccination course, 60 patients (17.65%) did not develop a protective antibody titer, with no statistically significant differences between the two groups (19.7% in cirrhotic vs 16.8% in non-cirrhotic;p=0.076). The majority of them (53/60 patients;88.3%) developed a protective titer after booster dose, without differences between cirrhotics and non-cirrhotics (p=0.089). At multivariate analysis, factors associated with a higher humoral response after booster dose were young age (p=0.0098);porto-sinusoidal vascular disorder (p=0.005), none or a single comorbidity rather than two or more (p=0.05) and Spikevax booster dose compared with Comirnaty (p=0.001). Moreover, the antibody titer is inversely related to age (p=0.000). Conclusions: In a large cohort of patients with CLD booster dose of anti-Sars-CoV-2 vaccine has an excellent immunogenicity and leads to an adequate antibody response even in those who had not produced a protective titer after the primary vaccination course. Cirrhosis is not associated with a reduced humoral response.
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Background: The emergence of the coronavirus disease (COVID-19) prompted pharmaceutical companies to develop effective vaccines to address the problem. While studies prove the vaccines are safe, rare systemic side effects remain possible. All types can cause various vaccine-related adverse reactions which are continuously being monitored. This paper aims to highlight new data on immunologic reactions to COVID-19 vaccines. Morphea demonstrated after COVID-19 vaccination is rare. Herein, we report a case of morphea that was most likely triggered by the immune response against inactivated COVID-19 vaccine. Method(s): A case of morphea was reviewed at the clinic in a tertiary hospital in the Philippines. Result(s): A 48 year old Japanese male had no underlying co-morbidities and no previous COVID-19 infection. He had his first dose of inactivated COVID-19 vaccine, coronaVac (sinovac) with no untoward reactions. After a month, he had his second dose. One week later, the patient started to have a red plaque on his upper back, palpable, tender on palpation and pruritic. Review of systems was unremarkable. The patient denied any insect bites or skin trauma. No medications applied or taken. No known allergies to food, medications or vaccines. He is a 32 pack years smoker. No family history of any autoimmune diseases. In five months, the skin lesion insidiously progressed, thickened and now spreading to the left side of the back. The patient sought consult with a dermatologist and rheumatologist. Physical examination revealed thickened skin and subcutaneous tissue on the upper back with post-inflammatory hyperpigmentation. Work-up showed normal complete blood count, normal chest x-ray, non-reactive Hepatitis B antigen. Antinuclear antibody (ANA) was positive with 1:80 titer and nuclear speckled pattern. Anti-double stranded DNA (anti-dsDNA), anti-smith, antinuclear ribonucleoprotein (anti-RNP), anti-SSA, anti-SSB and anti-Jo- 1 were all negative. The patient's skin biopsy to the reticular dermis showed findings that are consistent with Morphea. The patient was then started on Methotrexate. Conclusion(s): People should be educated about the possible outcomes of COVID-19 vaccines. One of these are immune-related diseases, such as morphea. The underlying mechanism of morphea is multifactorial but one hypothesis highlighted that the spike glycoprotein from vaccination drives these skin reactions. Other studies demonstrated molecular mimicry to viral epitopes. Discussing this cutaneous manifestation secondary to COVID-19 vaccine stressed the importance of this clinical condition, in order to provide a proper diagnosis and therapeutic management. Although there are novel case reports of morphea induced by COVID-19 mRNA vaccine, inactivated COVID-19 vaccine-related morphea has not been reported yet.
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Background: Adapted anti-SARS- CoV- 2 vaccination schedules have been recommended for patients with IMID due to a higher risk of reduced vaccine response. Nonetheless, there is little data on how different vaccine schedules influence immune responses and on the long-term persistence of vaccination responses in this subset. Purpose(s): The aim of this study is to assess the long-term course of humoral responses to SARS-CoV- 2 vaccines in a large prospective cohort of IMID patients and non-IMID controls with up to 10 months of follow-up following the first vaccine dose. Method(s): In February 2020, we started a prospective cohort of IMID patients and healthy controls (HC) to evaluate immune responses to SARS-CoV- 2 vaccines and infection (1). Individuals who provided data starting 4 weeks before their first vaccination and forward were included. Serum anti-SARS- CoV- 2 spike protein IgG were measured by ELISA (EUROIMMUN, Lubeck, Germany) in units of Optical density (OD) at 450 nm. An OD <1.1 was considered as poor response. We used time splines to fit linear mixed-effect models for log-transformed antibody levels and logistic mixed-effects models, adjusting for age and sex to estimate marginal mean antibody levels and adjusted risk of poor response with 95 percent confidence intervals. Antibody levels of twice-vaccinated patients were also compared to those who received 3 vaccinations. Result(s): Between December 2020 and December 2021, 3733 IMID patients and HC contributed 5564 samples, with a median (IQR) follow-up of 23.3 (13.9-0.9) weeks following first immunization (Table 1). By the date of their most recent sampling, 3280 (88%) participants had received two vaccines and 241 (6%) received three. Age and sex-adjusted estimated marginal mean IgG in IMID patients declined after week 10 and were significantly lower at all timepoints compared to controls (Figure 1A, Table 1). Adjusted risk of poor response at week 40 was 2.9% (1.4%-6.1%) in HC whereas 26.1% (15.8-40.0) in IMID (Figure 1B). After a median 20 (10-26). weeks from the second dose, 147 (6%) IMID patients had received a third dose. Adjusted mean antibody levels at 40 weeks in IMID patients who received three vaccine doses were higher than in HC who received two doses (Figure 1C). Conclusion(s): IMID patients had a weaker humoral response to SARS-CoV- 2 vaccination than controls at all time points following the first dose with a high risk of poor response at 40 weeks. Nonetheless, a third dose in IMID patients could provide higher antibody levels compared to unboosted healthy individuals.
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During these two years, the SARS-CoV-2 pandemic spread fast, killing people as surely as the global war. Step by step, research revealed several aspects of this plague. Understanding the essential etio-pathological characteristics of SARS-CoV-2 infection is necessary to outline discuss and assess its pathogenic mechanism and proceed with proper viral be-haviours assessment. Coronaviruses are enveloped by positive-sense and negative-sense RNA viruses. Their characteristic is a characteristic long spike protein projecting from the surface. These viruses have an unusual huge RNA genome (that is up to 33.5 kilobases). These viruses are the largest Noroviruses;the order includes Coronaviridiae and includes the order which includes the Coronaviridae, Arteriviridneae, Mesonivirideae, and Ronivirideae families. Coronaviruses have two subfamilies, Corinaviridea Orthocoronavirinae and Torviridiae Letovirinae. The taxonomy subdivides Orthocoronavirinae Coronaviridiae into different genera, e.g., the alfa, the beta, and gamma Coronaviruses. The coronavirus virion structure of coronaviruses is spherical with a diameter of 125 nm. Copyright © 2022 Phcog.Net. All rights reserved.
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Background: Since December 2019, COVID-19 has become a new health crisis in the world and has been declared a public health emergency of international concern by WHO. In search of anti-COVID treatment regimen, we applied molecular docking approach in order to identify the natural compounds that may have potential for anti-COVID treatment with specific target and selective inhibitory mechanism. Our goal is to identify the potential anti-COVID compounds based on virtual screening of the protein of spike glycoprotein as virtual inhibition target. Method(s): Molecular docking was carried out by using Molergo Virtual Docker. 35 compounds from different plant sources were selected and docked in the enzyme pocket. Result(s): The docking result revealed that some of the compounds exhibited good potency against the virus and can be used further for developing new drug regimen. Conclusion(s): The compounds of natural origin could be a good target and can be used as lead compounds for the treatment of this dreadful disease. Copyright © 2023 Bentham Science Publishers.
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Aim: The experiments aimed to document the presence of the ACE2 receptor on human muscle cells and the effects of the interaction of these cells with the spike protein of the SARS-CoV-2 virus in terms of induction of pro-inflammatory proteins, as well as to assess the possibility of reducing the pool of these proteins with the use of graphene oxide (GO) flakes. Methods: Human Skeletal Myoblast (HSkM), purchased from Gibco were maintained in standard condition according to the manufacturer's instruction. The cells were divided into 4 groups; 1. C-control, 2. S-with addition of spike protein, 3. GO-with the addition of graphene oxide, 4. GO-S-with addition of GO followed by the addition of S protein. Protein S (PX-COV-P049) was purchased from ProteoGenix (France). GO was obtained from Advanced Graphene Products (Zielona Gora, Poland). The influence of all the factors on the morphology of cells was investigated using light and confocal microscopy. ACE2 protein expression on muscle cells was visualized and 40 pro-inflammatory cytokines were investigated using the membrane antibody array method. The protein profile of the lysate of cells from individual groups was also analyzed by mass spectrometry. Conclusion: The experiments confirmed the presence of the ACE2 receptor in human skeletal muscle cells. It has also been documented that the SARS-CoV-2 virus spike protein influences the activation of selected pro-inflammatory proteins that promote cytokine storm and oxidative stress in muscle cells. The use of low levels of graphene oxide does not adversely affect muscle cells, reducing the levels of most proteins, including pro-inflammatory proteins. It can be assumed that GO may support anti-inflammatory therapy in muscles by scavenging proteins that activate cytokine storm.
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The COVID-19 pandemic has become a major human health concern. The pathogen responsible for COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), invades its host through the interaction of its spike (S) protein with a host cell receptor, angiotensin-converting enzyme 2 (ACE2). In addition to ACE2, heparan sulfate (HS) on the surface of host cells also plays a significant role as a co-receptor. In this study, SARS-CoV-2 SP receptor binding domain (RBD) wild type (WT), Delta and Omicron variants were expressed in Expi293F cells and used in the kinetic and structural analysis on their interactions with heparin by Surface plasminogen resonance (SPR). Detailed kinetic and structural analysis of the interactions of SARS-CoV-2 SP RBDs with heparin provides important information for designing anti-SARS-CoV-2 molecules.
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Tens of thousands of 3D structures of oligosaccharides have been deposited into the Protein Databank (PDB), representing hundreds of thousands of hours of effort by crystallographers. Yet, despite the critical importance of these structures in furthering the development of glycomimetic drugs, in explaining the activity of glycan-processing enzymes, and in providing a deeper understanding of the properties of glycoproteins and vaccines, they remain unnecessarily difficult to locate within the PDB. Part of this is due to limitations in searching for oligosaccharides on the PDB website, even after a recent carbohydrate remediation project completed by the PDB. While several databases have been reported that contain carbohydrate structural information extracted from the PDB, few offer flexible search capabilities and even fewer provide independent assessment of data quality. Here we present the GlyFinder and GlyProbity webtools (glycam.org/gf) and illustrate their application to locating oligosaccharides, carbohydrate derivatives, and glycoproteins stored in the PDB. We highlight the utility of curating the data on the basis of the theoretical conformational (CHI) energies [1] of the glycosidic linkages and illustrate how the deposited data can be employed to generate 3D models of glycoproteins, including the SARS-CoV-2 Spike protein [2].
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Introduction. There are few studies that evaluated the response to Covid- 19 vaccines, in primary Sjogren's Syndrome (pSS) and none evaluated ChAdOx1 n-Cov19 (AstraZeneca/Fiocruz). The aim of this study was to evaluate the efficacy and safety of the ChAdOx1 n-Cov19, a viral vector vaccine, in pSS compared to healthy control (HC). Methods. Patients with pSS >18 years, classified according to ACR/EULAR 2016 were included. Neutralizing antibodies against the Receptor Binding Domain - RBD portion of the Spike protein of SARS-CoV-2 (IgGS) were measured by chemiluminescence (Abbott), before the first dose (D0) and 28 days after the second dose (D28*). The test is considered reactive if >50 AU/ml. Results. Sixty pSS patients and 62 HC were recruited from a single center (HUCAM-UFES, Vitoria, ES, Brazil). The HC group was homogeneous for sex (92% women) and younger than HC (47+/-11 vs. 39+/-13, p<0.05). In the pSS group, 45.2% were anti-Ro positive, mean ESSDAI was 3.2, 83.3% were using DMARD or immunosuppressant/biological therapy, 31.9% were in high immunosuppression. The frequency of mild adverse events (AE) was similar in both two groups. No serious AE, hospitalizations or death were reported. There was no difference between the PGA ("Patient's Global Assessment") after vaccination (4.5 vs.5, p=0.903). Among seronegative individuals at baseline, the seroconversion rate (100% vs. 89%, p=0.02) was lower, and geometric mean titers (GeoMean IgG-S) was similar in pSS=696.9(CI95%237.6 -2,043) compared to HC=1,986(CI95%1,463-2,697;p=0.316). However, in those with high immunosuppression, the seroconversion (71%, p=0.001) and GeoMean titers were lower 229.4 (CI95%14.64-3,594, p=0.004). Patients in moderate to high disease activity (ESSDAI >=5) showed lower seroconversion (60%, p=0.006) and Geomean titers 31.7 (CI95%0.06-15.4;p=0.004). Conclusions. ChAdOX1 vaccine is safe and induced high GeoMean neutralizing antibodies titers and seroconversion rate in pSS patients similar to HC. Immunossuppression therapy and disease activity decreased the immune response to the vaccine.
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Introduction. Vaccination against SARS-CoV2 is beneficial for patients with autoimmune disease. Therefore, we recommended basic immunization as soon as it has become available for our patients. We preferred mRNAbased vaccination based on the international recommendations. However, several patients received other types of vaccines at their own or their general practitioner's discretion. Based on the antibody levels against the SARSCoV2 spike protein measured at the Institute of Laboratory Medicine of our university, we were able to draw initial conclusions about the effectiveness of vaccination regarding our primary Sjogren's syndrome patients. Patients and methods. Antibodies to SARS-CoV2 spike protein were analyzed in the sera of 77 patients with primary Sjogren's syndrome after being vaccinated with two doses between 1st January and 30th April, 2021, at least 30 days after the second vaccination. Antibody responses were classified as high (above 250 U/ml), moderate (between 50 and 250 U/ml) and low (below 50 U/ml). Relying on the SPSS statistical program, we were seeking correlations between the serum levels and the EULAR Sjogren's syndrome disease activity index (ESSDAI) and the potential influence of the different immunosuppressive treatment modalities, respectively. For the statistical analysis, chi2 tests were performed. Result(s): Pfizer vaccine was given to 58 patients, and the rest of our cohort received Moderna (2 patients), Sinopharm (10 patients), Astra Zeneca (6 patients) and Sputnik vaccine (1 patient). High antibody levels were found in 54 subjects (70.1%), moderate levels in 11 subjects (14.3%), and low levels in 12 subjects (15.6%). After having received the Pfizer vaccine, 86.2% had high, and only 5.2% had low antibody levels. One patient vaccinated with Moderna had high, while the other had low antibody level. The majority (55%) of those vaccinated with Astra Zeneca achieved high titers, and 17% were classified as low responders. After immunization with Sinopharm vaccine, 20% of the patients were classified into moderate response category, while the rest (80%) presented low antibody levels. We also measured low value in the serum of the patient that received the Sputnik vaccine. Serum levels of specific antibodies in patients not receiving any specific therapy (14 subjects) did not differ significantly from those treated with antimalarials (18 subjects), methotrexate (19 subjects), azathioprine (6 subjects), or low-dose steroids (20 subjects). Based on our results, the type of immunosuppressive treatment had less effect on the protection developed than the type of vaccination. There was no significant correlation between Sjogren's syndrome disease activity and the degree of specific antibody response to the vaccine. Conclusions. Our initial results suggest that the use of COVID vaccines is safe and effective for Sjogren's syndrome patients, regardless of the treatment used or of the ESSDAI.
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The year 2019 is a outbreak year during which the whole globe has suffered from Covid19 pandemic which has been spotted initially in China and later spread to the whole world;as a result of this viral disease, the whole world had shut down affecting billions of people but till today the Covid battle is on and people are suffering not only from this disease but also in terms of economy, starving being jobless etc. This paper briefs about Corona virus, its types, and structure;the replication and spreading of this virus, Covid19 detection methods, research on vaccination developed across the world to curb this virus;virus impact on various sectors, precautions to be taken to stay away from this virus and Ayurvedic remedy for it. The waves of corona had taken many lives on the globe & have its effect on life style of people. To curb this virus, prevention vaccination has to be found and we people must change in a way so that we could avoid future consequences for the upcoming generation. Keywords.
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Introduction: The emergence of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) as a pandemic has put the global population at risk for its infection. It has also led to an accelerated effort to develop vaccines that can mitigate progression to severe infections at a minimum. The ambiguity about existence of antibodies in the human serum poses problem in formulating public health policies like suitable interval between doses of vaccines, appropriate time for vaccinating population, post natural infection, necessity of booster doses along with single dose. Aim: To estimate neutralising antibody level following vaccination of Healthcare Workers (HCWs) after three months and six months respectively. Materials and Methods: This was a prospective observational study performed in Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India after Institutional Ethics Committee (IEC) approval from January 2021 to February 2022. The study was conducted in 304 HCWs in the institute who had received two doses of Recombinant ChAdOx1 nCoV- 19 Corona Virus Vaccine (Covishield). 41 HCWs who were naturally infected with SARS-CoV-2 either before or after vaccination were also included. These participants were then subjected to IgG neutralising antibody titer estimation at three months and six months, postvaccination. Results: The study included 304 eligible HCWs. Majority of the participants belonged to the age group of 31-40 years (35.9%). Majority of the study participants were females (51%). Of the 304 participants, 263 were uninfected and 41 participants had been infected before and after vaccination. At the six month follow-up, it was observed that all but one HCW had seroconverted with majority of the participants showing more than 60% antibody level. Participants in the age group of 31-40 years showed the highest level and this observation was found to be statistically significant. Conclusion: Neutralising antibody response in HCWs is a key indicator of the efficacy of the vaccination program for Coronavirus Disease-2019 (COVID-19) in India.
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Introduction: The SARS-CoV-2 pandemic killed over 6 million people worldwide. Children were described to have predominantly mild or asymptomatic infections and to be less exposed to the virus, at least for the initial variants. In the present study, we describe how SARS-CoV-2 can silently infect tonsils and adenoids in children undergoing adenotonsillectomy. Method(s): In this cross-sectional study we assessed children who underwent adenotonsillectomy between October 2020 and September 2021 in a secondary hospital in Brazil. All the caregivers denied any symptom of acute viral upper airway infection in the month prior to surgery. Briefly, nasal cytobrush (NC), nasal wash (NW) and tonsillar tissue fragments posttonsillectomy were tested by RT-PCR, immunohistochemistry (IHC), in situ immunofluorescence (IF), and flow cytometry. Result(s): A total of 48 children (18 females, median age 5.5 years) were enrolled. None of them had been vaccinated against COVID-19 at the time of surgery. Only 2 had a history of previous COVID-19 diagnosis, 3 and 5 months, respectively, before surgery. SARS-CoV-2 RNA was detected in 25% (12) of patients-20% in palatine tonsils, 16.27% in the adenoids, 10.41% in NC, and 6.25% in NW. IHC labeling showed viral nucleoprotein presence in both adenoids and palatine tonsils, in epithelial surface and lymphoid cells from extrafollicular and follicular regions. In 5 out of 7 patients, in situ IF showed the expression of ACE2 and TMPRSS2 and viral spike protein in the tonsillar tissue. Flow cytometry revealed that SARS-CoV-2 is predominantly observed in CD123+ dendritic cells (10.57% of all tested sites), followed by CD14+ monocytes (6.32%). Conclusion(s): According to these results, the prevalence of SARS-CoV-2 infection seems to be higher than expected and underdiagnosed in children at this age group. Palatine tonsils and adenoids are important sites of infection and may be a reservoir for the virus. Nevertheless, it is still unclear the impact of these results on virus transmission.
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The Spike domain of SARS-COV-2 binds ACE2 and induces peptidase internalization removing a key regulatory site within the renin-angiotensin system that may exacerbate the effects of SARS-COV-2. However, a recent study finds that an early Beta variant (D614G) of the SARS-COV-2 Spike protein and its receptor-binding domain (RBD) markedly stimulated ACE2 activity using fluorescent substrates. The more dominant forms of SARS-COV-2 include the Delta and Omicron variants and we determined whether these new variants activate ACE2. Delta (B.1.617.1) and Omicron (B.1.1.529) RBDs, and Beta Spike (B1.351) were incubated with human soluble ACE2 for 10 mins at 37degreeC followed by Ang II [2 muM] and 125I-Ang II [0.5 nM] for up to 20 mins, and the Ang-(1-7)/Ang II ratio quantified by HPLC-gamma detection. Ang-(1-7)/Ang II increased linearly over time and doubled with 10 ng of ACE2 (*P<0.01 vs 5 ng;N=4);however, the Delta or Omicron RBD proteins (1 muM) failed to stimulate ACE2 activity at any time point (A). Varying concentrations of the Delta or Omicron RBDs, as well as Spike protein also failed to stimulate ACE2 activity (5 ng), although 200 nM Omicron RBD was inhibitory (B). The newer Spike variants may not activate ACE2;however, the Spike D614G variant also failed to activate ACE2, which questions whether SARS-COV-2 enhances ACE2 activity to metabolize Ang II. We conclude that Delta and Omicron variants do not stimulate the metabolism of Ang II to Ang-(1-7). Moreover, alterations in circulating ACE2 activity in COVID-19 patients likely reflect changes in protein content through shedding of the peptidase, although the interaction of ACE2 autoantibodies to influence peptidase activity is also possible. (Figure Presented).
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The United Kingdom this week became the first country to approve an updated COVID-19 booster directed at two different strains of the coronavirus. The "bivalent" booster, made by Moderna, will have the same dose of messenger RNA as the company's prior boosters but will target both the original version of the coronavirus and the first Omicron variant, BA.1, which emerged in late 2021. Clinical trials and other research by Moderna suggest its retooled booster generates a stronger immune response against BA.1 and other versions of Omicron now in circulation than its existing vaccine, introduced in December 2020. The new shot will be available in the fall. A similar booster is expected in the United States, although in June the Food and Drug Administration asked Moderna and a second manufacturer, Pfizer, to include the spike protein component for more recent versions of Omicron, BA.4 and BA.5, rather than BA.1. Copyright © 2022 American Association for the Advancement of Science. All rights reserved.
ABSTRACT
Purpose: Administration of mRNA-based SARS-CoV-2 vaccines confers protection from SARS-CoV-2 infection and reduces its severity in the general population. It has been suggested that mounting a coordinated adaptive immune response characterized by production of neutralizing antibodies and SARS-CoV-2 spike proteinspecific T-cells correlates with protection from infection. Studies in organ transplant recipients have demonstrated suboptimal responses after 2 doses of SARS-CoV-2 vaccination;however, the impact of different immunosuppressive regimens (IS) on T-cell responses is not well described. This study prospectively evaluated the impact of IS on T-cell responses in a kidney transplant (KTx) population and compared these to 26 healthy controls. Method(s): In this single-centre, prospective study, 92 KTx on follow-up at our centre were enrolled after informed consent. T-cell responses were evaluated before and after each of 2 doses of BNT162b2 SARS-CoV-2 vaccine administered 21 days apart: before each dose, 10-14 days after Dose1 and 21-24 days after Dose2. The study population included 69.6% Live-Donor and 30.4% Deceased-Donor KTx. Longitudinal assessment of the quantity of spike-specific T-cells was performed by stimulating whole blood with peptides covering the SARS-CoV-2 spike protein, followed by cytokine (IFN-gamma, IL-2) measurement (JCI, Tan et al, 2021). KTx were stratified by maintenance IS into 4 groups and T-cell responses compared between groups. Result(s): As shown (Figures 1A, 1B), in comparison to healthy controls, KTx displayed poor spike-specific T-cell responses as measured by IFN-gamma and IL-2 release. Percent responders were significantly lower for KTx vs. healthy controls: 6.5% vs. 92.3% after Dose1 (P<0.00001) and 27.2% vs. 100% after Dose2 respectively. There was a significant impact of different IS regimens (Figure 1C);percent responders after Dose2 were 19%, 43%, 40% and 71% for KTx receiving CNI-MPA-Pred, CNI-Aza-Pred, mTORi and Other regimens respectively (P=0.013). Conclusion(s): Our results highlight the critical role of IS on T-cell responses to SARS-CoV-2 vaccination. In the context of the COVID-19 pandemic, monitoring T-cell and antibody responses over time after vaccination, modulating IS and modifying vaccination strategies are clearly needed to protect this vulnerable population.