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BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease, which presents an immune disorder that leads to the production of autoantibodies with potential involvement of multiple organs. Infections are one of the most frequent causes of hospitalization and death in lupus patients, and SARS-CoV-2 infection has been a global threat since March 2020. Immunization of these patients has been strongly recommended, although vaccine evaluation studies have not included this profile of patients.ObjectivesTo evaluate the immunogenicity and safety after 2 doses of the vaccine against SARS-CoV2 in patients with SLE.MethodsSubgroup of SLE patients from the prospective multicenter cohort of patients with immune-mediated diseases "SAFER” – Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease, a phase IV study. Vaccination against SARS-CoV-2 took place with vaccines approved by Brazilian regulatory bodies CoronaVac (Inactivated SARS-CoV-2 Vaccine), ChadOx-1 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) and this project followed in line with the guidelines of the National Immunization Plan in Brazil. Patients aged 18 years or older with a previous diagnosis of SLE (according to the 2019 ACR/EULAR criteria) were included. Patients were evaluated by telephone contact and in a face-to-face visit on the 28th day after each dose. Patients were followed up by means of blood collection for measurement of IgG antibody against SARS-COV-2 by chemiluminescence and disease activity assessed using SLEDAI-2K score.ResultsA total of 367 individuals with SLE were included, of whom 207 received 2 doses of CoronaVac, 128 received 2 doses of ChadOx-1 and 32 received 2 doses of BNT162b2. 90% of the subjects were female with a mean age of 37 years. About 42% (154) of the individuals included did not have any other associated comorbidity. 50% (182) of patients were using oral glucocorticoids and azathioprine was the most frequent immunosuppressive therapy. Regarding disease activity parameters, 38% (140) of patients had zero SLEDAI-2K at baseline and 41% (147) had zero SLEDAI-2K 28 days after the 2nd dose. Anti-DNA positivity was 30.7% (16/52) at inclusion and 32.6% (17/52) 28 days after the 2nd dose. Complement consumption was present in 18% (10/55) at inclusion and in 14.5% (8/55) 28 days after the 2nd vaccine dose. The geometric mean titers of IgG antibodies against SARS-COV-2 increased in the different vaccine groups, log 2.27 BAU/mL at inclusion and log 5.58 BAU/mL 28 days after the 2nd dose. Antibody titers after second dose varied between different vaccines, 4.96 BAU/mL CoronaVac, 6.00 BAU/mL ChadOx-1 and 7.31 BAU/mL BNT162b2 vaccine, p < 0.001. Only 3.54% (13/367) patients had covid-19 infection after the 15th day of the second dose of immunization, 9 of them having received 2 doses of CoronaVac, 4 of them of ChadOx-1 and none of them receiving BNT162b2, with p-value of 0.63.ConclusionThis study suggests that vaccines against SARS-COV-2 are safe in SLE patients. Induction of immunogenicity occurred in different vaccine regimens. Only 3.5% of individuals had COVID-19 infection with no difference between the types of vaccines evaluated. Future analyzes to explore the association of the effect of immunosuppressive medication, as well as the impact of booster doses and longer follow-up on clinical outcome will be performed.References[1]Mason A, et al. Lupus, vaccinations and COVID-19: What we know now. Lupus. 2021;30(10):1541-1552.[2]Furer V, Eviatar T, Zisman D, et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: A multicentre study. Ann Rheum Dis. 2021;80(10):1330-1338.[3]Izmirly PM, Kim MY, Samanovic M, et al. Evaluation of Immune Response and Disease Status in SLE Patients Following SARS-CoV-2 Vaccination. Arthritis Rheumatol. Published online 2021.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundUnderstanding the dynamics of humoral immunity after COVID-19 vaccination is crucial in developing vaccination strategies. Antibody response patterns are more complex in patients with rheumatoid arthritis (RA) because of their underlying autoimmunity and immunosuppressive medications. The kinetics of vaccine response in RA patients are not well understood.ObjectivesTo construct a model of antibody response to COVID-19 vaccination in patients with RA.MethodsTwo patient groups were included for the study. The first group was composed of RA patients who were enrolled for influenza vaccination study between Oct 6, 2021 and November 3, 2021, in whom serial serum samples were obtained 0, 4, 16 weeks after vaccination. The second group was consecutively enrolled from outpatient clinic between October 6, 2021 and June 3, 2022, in whom serum sample was obtained once. After collecting data on demographics, vaccination and infection history of COVID-19 were obtained by self-report via questionnaire and data from Korean center for disease control. We then measured antibody titers against receptor binding domain of spike protein (anti-RBD) and nucleocapsid (anti-N), using Chemiluminescence microparticle immunosaasy (Abbott, USA) and Electrochemiluminescence immunoassay (Roche, Germany) respectively. The anti-RBD titer was log-transformed to improve normality. Time from vaccination and log of anti-RBD titer was modeled using fractional polynomial. Covariates including age, sex, BMI, underlying disease and immunosuppressive drugs were analyzed using Generalized Estimating Equations to account for repeated measured from a subject.ResultsA total of 736 patients (1042 samples) were enrolled. After excluding patients who experienced COVID-19 infection before sampling (n=84), those unvaccinated (n=44) and uncertain COVID-19 infection history (n=59), the data on 778 samples from 549 patients were analyzed (Group 1: 125, Group 2: 424). Antibody titer reached peak at 12 days after vaccination and decreased exponentially (Figure 1) which fell to 36.5% from peak after 2 months. Compared to the first vaccination, the 3rd and 4th vaccination significantly shifted anti-RBD antibody response curve (28 times, 95% CI 4~195;32 times 95% CI 4~234, respectively). However, there was no significant shift after the 4th vaccination from the 3rd vaccination (p=0.6405). Multivariable analysis showed that number of vaccinations and sulfasalazine (coefficient: 0.40, 95% CI 0.12~0.68) increased vaccine response but age (coefficient: -0.03, 95% CI -0.04~-0.02), abatacept (coefficient: -2.07, 95% CI -3.30~-0.84) and, JAK inhibitor (coefficient: -0.82, 95% CI -1.34~-0.31) decreased vaccine response.ConclusionAnti-RBD response to COVID-19 vaccination showed a peak at 12 days after vaccination and then exponentially decreased in patient with RA. The antibody response is affected by age and medications used for the treatment of RA.Table 1.ln[RBD (U/ml)]coefficient (univariable)95% CIp-valuecoefficient (multivariable)95% CIp-valuesex (female)0.17-0.22, 0.550.393---age-0.02-0.03, -0.01<.001**-0.03-0.04, -0.02<.001**DM0.11-0.27, 0.500.568---HTN-0.38-0.69, -0.070.018*---CKD0.680.07, 1.290.030*---RA duration (yr)-0.04-0.06, -0.010.001**---Pd (mg/d)-0.06-0.11, 0.000.035*---MTX use-0.23-0.52, 0.050.105---HCQ use0.01-0.28, 0.290.965---SSZ use0.450.07, 0.840.022*0.400.12,0.680.005**LEF use0.00-0.37, 0.370.988---TNF inhibitors use0.29-0.16, 0.730.208---Abatacept use-2.07-3.14, -0.99<.001**-2.07-3.30, -0.840.001**JAK inhibitors use-0.88-1.52, -0.240.007**-0.82-1.34, -0.310.002**Time (months)log(t)-1.96-2.37, -1.54<.001**-1.90-2.29, -1.50<.001**t
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BACKGROUND: The coronavirus disease 2019 (COVID-2019) causes the severe contagious acute respiratory syndrome. Therefore, massive vaccination campaign is mandatory to control the spread. Sputnik COVID-19 vaccines induce immunity through different mechanisms involving antibody response that bind to the spike protein to neutralize the viral entry into the cells. AIM: This study aims to compare the titers of specific antibodies in the pre-and post-vaccination sera in the vaccinated Egyptian population to evaluate the efficacy of the sputnik vaccine. METHOD(S): Samples were collected from 205 adult volunteers receiving the Sputnik vaccine in the Reference Laboratory of Egyptian University Hospitals. Samples were collected before vaccination and within 1, 2, or 3 months after receiving two doses of Sputnik SARS-CoV-2 vaccines from August to October 2021, serum samples collected were tested by quantitative chemiluminescent immunoassay using (Mindray CL-960i chemiluminescence analyzer, India) at the Reference laboratory of Egyptian University Hospitals for neutralizing antibodies, anti-spike antibodies, and total antibody levels before and after vaccination. RESULT(S): The results of the 205 paired samples illustrated that there was a statistically significant difference between pre-and post-vaccination antibody levels with a p-value of (< 0.001) indicating that the vaccine produced significantly high levels of antibodies. CONCLUSION(S): COVID-19 Sputnik vaccines induce immunity through an antibody response that binds to the virus to neutralize its entry into cells. Our study showed a significant increase in the measured post-vaccination levels of the three antibodies among the enrolled volunteers compared to the basal pre-vaccination level and thus sputnik vaccine protects against SARS-CoV-2 infections.Copyright © 2023 Ghada Ismail, Dalia Abdelhamid, Marwa Salah Mostafa, Noha Alaa Eldin Fahim, Ahmed Elshafei, Hossam Abdelghaffar, Nashwa Naguib, Omnia Taher, Menna Asker.
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Objective: During the COVID-19 pandemic, cancer patients had restricted access to standard of care tissue biopsy. Liquid biopsy assays using next generation sequencing technology provides a less invasive method for determining circulating tumour mutations (ctDNA) associated with targeted treatments or prognosis. As part of deploying technology to help cancer patients obtain molecular testing, a clinical program was initiated to offer liquid biopsy testing for Canadian patients with advanced or metastatic breast cancer. Method(s): Blood was drawn in two 10 mL StreckTM DNA BCTs and sent to the CAP/CLIA/DAP accredited Imagia Canexia Health laboratory for testing using the clinically validated Follow ItTM liquid biopsy assay. Plasma was isolated using a double spin protocol and plasma cell-free DNA (cfDNA) extracted using an optimized Promega Maxwell RSC method. Extracted cfDNA was amplified using the multiplex amplicon-based hotspot 30 or 38 gene panel and sequenced. An inhouse developed bioinformatics pipeline and reporting platform were used to identify pathogenic single nucleotide variants (SNVs), indels (insertions and deletions), and gene amplification. Included in the panel are genes associated with metastatic breast cancer: AKT1, BRAF, ERBB2, ESR1, KRAS, PIK3CA, TP53. Result(s): To identify biomarkers, 1214 metastatic or advanced breast cancer patient cfDNA samples were tested. There were 15 cases sent for repeat testing. We reported 48% of samples harboring pathogenic ctDNA mutations in TP53 (22%), PIK3CA (19%), ESR1 (18%), AKT1 (2%), ERBB2 (1.5%). Co-occurring variants were identified in samples with ESR1/PIK3CA as well as TP53/PIK3CA (both p-values <0.001). Interestingly, 29% of samples with mutated ESR1 harbored >= 2 ESR1 ctDNA mutations. In 56% of cases, previous molecular testing indicated the cancer subtype as hormone receptor (ER, PR) positive with/without HER2 negative status. In this specific subgroup, 49% harbored ctDNA mutations with 63% of those being PIK3CA and/or ESR1 mutations. Conclusion(s): A population of Canadian women with metastatic breast cancer were tested using a liquid biopsy gene panel during the COVID-19 pandemic for identification of biomarkers for targeted therapeutic options. Over 50% of the samples were identified as hormone positive, with greater than 60% harboring PIK3CA and ESR1 ctDNA mutations. Studies have shown that metastatic PIK3CA mutated ER-positive/HER2-negative tumors are predictive to respond to alpelisib therapy and have FDA and Health Canada approval. Additionally, ESR1 mutations are associated with acquired resistance to antiestrogen therapies, and interestingly we identified 29% of ESR1 mutated samples with multiple mutations possibly indicating resistance subclones. In future studies, longitudinal monitoring for presence of multiple targetable and resistance mutations could be utilized to predict or improve clinical management.
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Introduction In this study, we aimed to monitor anti-spike and anti-nucleocapsid antibodies positivity in healthcare workers (HCWs) vaccinated with two doses of inactivated CoronaVac (Sinovac, China) vaccine. Methods Overall, 242 volunteer HCWs were included. Of the participants, 193 were HCWs without history of prior documented COVID-19 (Group 1), while 49 had history of prior documented COVID-19 before vaccination (Group 2). The participants were followed up for SARS-CoV-2 antibodies positivity at four different blood sampling time points (immediately before the second vaccine dose and at the 1st, 3rd months and 141-150 days after the second dose). We investigated the serum IgG class antibodies against SARS-CoV-2 RBD region and IgG class antibodies against SARS-CoV-2 nucleocapsid antigen by chemiluminescent microparticle immunoassay (CMIA) method using commercial kits. Results We found positive serum anti-RBD IgG antibody in 76.4% of the participants (71% in Group 1;98% in Group 2) 28 days after the first dose. When the antibody levels of the groups were compared at the four blood sampling time points, Group 2 anti-RBD IgG levels were found to be significantly higher than those in Group 1 at all follow-up time points. Although anti-RBD IgG positivity persisted in 95.6% of all participants in the last blood sampling time point, a significant decrease was observed in antibody levels compared to the previous blood sampling time point. Anti-nucleocapsid IgG antibody was positive in 12 (6.2%) of participants in Group 1 and 32 (65.3%) in Group 2 at day 28 after the first dose. At the fourth blood sampling time point, anti-nucleocapsid antibodies were found to be positive in a total of 20 (9.7%) subjects, 10 (6.1%) in Group 1 and 10 (23.8%) in Group 2. Conclusions In this study, it was determined that serum antibody levels decreased in both groups after the third month after the second dose in HCWs vaccinated with CoronaVac vaccine.Copyright © GERMS 2022.
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BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with comorbidities associated. However, few studies in the literature assessed the safety and immunogenicity of the COVID-19 heterologous vaccine schedules in patients with RA.ObjectivesEvaluate the safety and immunogenicity of two heterologous vaccine schedules against SARS-CoV-2 in patients with RA.MethodsThese data are from the study "SAFER - Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases,” a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Immunogenicity and adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 plus additional dose of BNT162b2 or after two doses of inactivated SARS-CoV-2 vaccine CoronaVac plus additional dose of BNT162b2. The titers of neutralizing antibodies against the receptor-biding domain of protein spike (S) of SARS-CoV-2 (anti-RBD) were measured by chemiluminescence test after each dose of immunizers. Proportions between groups were compared using the chi-square and Fisher's exact tests for categorical variables. Clinical Disease Activity Index (CDAI) before and after vaccination was assessed using the McNemar test.ResultsA total of 107 patients with RA were include in the study, most of them female, with a mean age of 46 years. Biological disease modifying anti-rheumatic drugs (DMARDs) were used by 50 % of the patients and conventional synthetics DMARDs in 48 %. Two doses of CoronaVac plus additional dose of BNT162b2 was used in 66 patients and two doses of ChAdOx1 plus additional dose of BNT162b2 in 41. Only mild AEs were observed, mainly after the first dose. The most common AEs after all doses, regardless of the immunizer type, were pain at the injection, headache, arthralgia and myalgia. ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0,001) and arthralgia (68% vs 15%, p < 0,001) compared to CoronaVac. No patients had flare after the vaccination. The titers of anti-RBD after two doses of ChAdOx1 were higher compared to two doses of CoronaVac (6,03 BAU/mL vs 4,67 BAU/mL, p < 0,001). However, after the additional dose of BNT162b2, the anti-RBD titers were similar in both groups (7.28 BAU/mL vs 7.06 BAU/mL, p = 0.56). Only two cases of COVID 19, with mild symptoms, were reported, one in each group.Figure 1.ConclusionChAdOx1, CoronaVac, and BNT162b2 vaccines are safe in RA patients. The frequency of local adverse effects, particularly pain at the injection site, is high. AEs are more frequent with ChAdOx1, especially after the first dose. The use of the immunizers does not change the degree of inflammatory activity of the disease. The immunogenicity of the two heterologous regimens analyzed was similar.References[1]Marques C, Kakehasi AM, Gomides APM, Paiva EDS, Dos Reis Neto ET, Pileggi GCS, et al. A Brazilian Cohort of Patients With Immuno-Mediated Chronic Inflammatory Diseases Infected by SARS-CoV-2 (ReumaCoV-Brasil Registry): Protocol for a Prospective, Observational Study. JMIR Res Protoc.[2]Medeiros-Ribeiro AC, Aikawa NE, Saad CGS, Yuki EFN, Pedrosa T, Fusco SRG, et al. Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial. Nat Med. 2021;27(10):1744-1751.[3]Machado PM, Lawson-Tovey S, Strangfeld A, Mateus EF, Hyrich KL, Gossec L, et al. Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry. Ann Rheum Dis. 2022;81(5):695-709.[4]Tavares ACFMG, Melo AKG, Cruz VA, Souza VA, Carvalho JS, Machado KLLL, et al. Guidelines on COVID-19 vaccination in patients with immunemediated rheumatic diseases: a Brazilian Society of Rheumatology task force. Adv Rheumatol. 2022;62:3.Acknowledg ments:NIL.Disclosure of InterestsNone Declared.
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BackgroundAnti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) is a small vessel vasculitis. Hallmarked by the presence of antibodies against antigens in cytoplasmic granules of neutrophils. Different microbiological agents and vaccines can trigger an AAV, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and Coronavirus disease 2019 (COVID-19) vaccine.ObjectivesTo compare: a) proportion of positive ANCA (+ANCA) test in 2019 (COVID-19 pre-pandemic) vs 2021 (COVID-19 pandemic), b) clinical features and c) vasculitis activity between vasculitis related to COVID 19 vaccination vs non-related.MethodsAll ANCA tests performed in 2019 and 2021 in a referral hospital were reviewed. Additionally, we studied 18 +ANCA patients diagnosed in 2021 and accepted to participate in present study. The patients were divided in two groups: a) +ANCA after SARS-CoV-2 mRNA vaccine (COVID-related) and +ANCA before COVID-19 vaccine (COVID-nonrelated). Diagnosis of underlying AAV was based on ACR/EULAR 2022 criteria. Disease activity was assessed with Birmingham Vasculitis Activity Score (BVAS). ANCA testing was done by chemiluminescence assay using IO-FLASH (Inova, San Diego, CA) according to the instructions of the manufacturer.ResultsANCA tests were positive in 14 of 1287 cases (1.1%) and in 32 of 1434 (2.2%) cases in 2019 and 2021, respectively (figure 1, the differences were statistically significant (p=0.020). The main features of 18 ANCA+ patients diagnosed in 2021 are summarized in table 1. COVID-19 related patients showed a median of 7 points on BVAS score compared of the median of 5 points on BVAS score on not related patients.ConclusionThere seems to be an increase of +ANCA at the expense of anti-PR3 antibodies following the COVID-19 vaccine. In patients with +ANCA following vaccination there seems to be an increased disease activity according to BVAS score without reaching statistical significance.References[1]Damoiseaux, J., et al Autoimmunity Reviews.2021. PMID 34896650.[2]Irure-Ventura, et al. IScience.2022. PMID 35937087.Table 1.Main general features of 18 patients with ANCA+ test diagnosed in 2021.FEATURESAll cases n= 18Related n= 13Non-related n= 5p*Age (years), mean±SD62±1767±15.352±16.50.167Male/ Female n, (% male)10/8 (55.6)9/4 (69.2%)1/4(20)0.067ANCA-test specificity, n (%)MPO-ANCA9 (50)7 (53.8)2(40)0.609PR3-ANCA8 (44.4)5 (38.5)3(60)0.423Both1 (5.6)1 (7.7)0-CRP (mg/dL), median [IQR]2,4 [0.4-10.7]3.8 [0.4-10.1]1 [0.4-10.9]0.802ESR, mm/1st hours, median [IQR]50 [25-104]47 [25.3-71.8]50 [25-120]0.634BVAS, median [IQR]6.5 [4.2-8]7 [4-8]5 [5-8]0.842FFS, n (%)03 (16.7)2 (15.4)1 (20)0.819≥115 (83.3)11 (84.6)4 (80)0.819ENT involvement, n (%)12(66.7)10 (76.9)2 (40)0.148MSK involvement, n (%)11(61.1)7(53.8)4 (80)0.322CNS/PNS involvement, n (%)10 (55.6)7 (53.8)3 (60)0.819Lung involvement, n (%)9 (50)6 (46.2)3 (60)0.609Kidney involvement, n (%)8 (44.4)7 (53.8)1 (40)0.208Ocular involvement, n (%)2 (11.1)2 (15.4)00.366Cutaneous involvement, n (%)2 (11.1)02 (40)0.019*p values according to Man Whitney test.Abbreviations (in alphabetical order):AAV: anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis;ACR: American college of Rheumatology;ANCA: Antineutrophil cytoplasmic antibody;BVAS: Birmingham Vasculitis Activity Score;CNS: central nervous system;CRP: C-Reactive protein;dL: deciliter;ENT: ear, nose, throat;ESR: erythrocyte sedimentation rate;FFS: Five-Factors Score;g;IQR: Interquartile range;mg: milligram;MSK: musculoskeletal;MPO-ANCA= ANCA specific for myeloperoxidase;n=Number;PNS: peripheral nervous system;PR3-ANCA= ANCA specific for proteinase 3;SD: Standard DeviationFigure 1.Comparison of ANCA test in 2019 and 2021.[Figure omitted. See PDF]Acknowledgements:NIL.Disclosure of InterestsFabricio Benavides-Villanueva: None declared, Vanesa Calvo-Río Speakers bureau: Dra V. Calvo had participation in company-sponsored speaker´s bureau from Roche, Novartis, Galápagos, UCB Pharma, MSD, Celgene, and Grünenthal and received support for attending m etings and/or travel from Janssen, Abbvie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer, Galápagos., J. Loricera Speakers bureau: Dr. J. Loricera had participation in company-sponsored speaker´s bureau from Roche, Novartis, Galápagos, UCB Pharma, MSD, Celgene, and Grünenthal., Consultant of: Dr. J. Loricera had consultation fees in company-sponsored speaker´s bureau from Roche, Novartis, Galápagos, UCB Pharma, MSD, Celgene, and Grünenthal and received support for attending meetings and/or travel from Janssen, Abbvie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer, Galápagos., Juan Irure-Ventura: None declared, Marcos Lopez-Hoyos: None declared, Ricardo Blanco Speakers bureau: Dr. R. Blanco had participation in company sponsored speaker´s bureau from Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Consultant of: Dr. R. Blanco had consultation from Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Grant/research support from: Dr. R. Blanco received grants/research supports from Abbvie, MSD and Roche.
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Intro: Different vaccines against COVID-19 have been approved by the World Health Organization (WHO) at different stages, however, limited data is available on long-term kinetics of antibodies induced by vaccines. This study was performed to investigate the persistence and dynamicity of BBV-152 (Covaxin)- and AZD1222 (Covishield)-induced immunoglobulin-G (IgG) antibodies over the year and neutralizing antibodies' status after the one-month post booster dose. Method(s): This 52-week longitudinal cohort study documented antibody persistence and neutralizing antibody status among 278 health-care workers (HCWs) from four different healthcare and research facilities in Odisha, enrolled in January 2021 and continued until March 2022. An automated chemiluminescence immune assay (CLIA) platform from Abbott Diagnostics was used to quantify IgG antibodies against SARS-CoV-2's spike receptor-binding domain (RBD) and a surrogate virus neutralization test (sVNT) was performed by enzyme-linked immunosorbent assay (ELISA). If any participants developed any symptoms of COVID-19, nasopharyngeal swabs were collected and sent to ICMR- RMRC, Bhubaneswar for RT-PCR confirmation. Finding(s): Among the 243 participants, 119 HCWs (48.97%) were Covaxin recipients and the remaining 124 (51.02%) were Covishield recipients. During the seven follow- ups, 104 participants (42.79%) were identified as vaccine breakthrough cases. In 139 non-infected HCWs, the median antibody titer significantly waned after ten months of double dose, both for Covaxin (342.7 AU/mL at DD1 vs 43.9 AU/mL at DD10) and Covishield (2325.8 AU/mL at DD3 vs 595.2 AU/mL at DD10). No statistically significant differences in antibody titers were observed based on age, gender, comorbidities, and blood groups. The median inhibition activity of sVNT was increased significantly for Covaxin and Covishield booster recipients. Among the booster dose recipients, 24 had breakthrough cases by the Omicron variant. Conclusion(s): Results of this longitudinal cohort study can be used to implement vaccination strategies and could also aid in tracking and designing vaccine mandates to minimize vaccine escape.Copyright © 2023
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Thrombotic thrombocytopenic purpura (TTP) is a prothrombotic condition caused by a significant deficiency of the enzyme, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). In the absence of adequate levels of ADAMTS13 (i.e., in TTP), plasma VWF accumulates, in particular as "ultra-large" VWF multimers, and this leads to pathological platelet aggregation and thrombosis. In addition to TTP, ADAMTS13 may be mildly to moderately reduced in a range of other conditions, including secondary thrombotic microangiopathies (TMA) such as those caused by infections (e.g., hemolytic uremic syndrome (HUS)), liver disease, disseminated intravascular coagulation (DIC), and sepsis, during acute/chronic inflammatory conditions, and sometimes also in COVID-19 (coronavirus disease 2019)). ADAMTS13 can be detected by a variety of techniques, including ELISA (enzyme-linked immunosorbent assay), FRET (fluorescence resonance energy transfer) and by chemiluminescence immunoassay (CLIA). The current report describes a protocol for assessment of ADAMTS13 by CLIA. This protocol reflects a rapid test able to be performed within 35 min on the AcuStar instrument (Werfen/Instrumentation Laboratory), although certain regional approvals may also permit this testing to be performed on a BioFlash instrument from the same manufacturer.
Subject(s)
COVID-19 , Purpura, Thrombotic Thrombocytopenic , Humans , Purpura, Thrombotic Thrombocytopenic/diagnosis , von Willebrand Factor , Luminescence , ADAM Proteins , COVID-19/diagnosis , ADAMTS13 ProteinABSTRACT
As the vaccine was successfully developed, the spread of the epidemic (COVID-19) was effectively controlled. But there are still thousands of people affected COVID-19 after being vaccinated. Neutralizing activity has become a critical method for quantifying neutralizing antibody against SARS-CoV-2. However, limited to the strict conditions of cold chain transportation, the neutralizing activity test has not been widely promoted. In this study, a room-temperature-storable chemiluminescence freeze-drying mixes for SARS-CoV-2 neutralizing antibody detection was developed to decrease the cost of lyophilization step for promoting its application in third world countries. Several freeze concentrated solutions were used to protect the antigen bioactivity. The mixes can be stored at room temperature over 12 months and still exhibited great accuracy and precision. Thus, the proposed room-temperature-storable chemiluminescence freeze-drying mixes offers a cheap and stable storage method for SARS-CoV-2 neutralizing antibody detection and shows a great potential for promoting the neutralizing activity test.
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PurposeThis study aims to estimate the overall SARS-CoV-2 seroprevalence and evaluate the accuracy of an antibody rapid test compared to a reference serological assay during a COVID-19 outbreak in a prison complex housing over 13,000 prisoners in Brasília.Design/methodology/approachThe authors obtained a randomized, stratified representative sample of each prison unit and conducted a repeated serosurvey among prisoners between June and July 2020, using a lateral-flow immunochromatographic assay (LFIA). Samples were also retested using a chemiluminescence enzyme immunoassay (CLIA) to compare SARS-CoV-2 seroprevalence and 21-days incidence, as well as to estimate the overall infection fatality rate (IFR) and determine the diagnostic accuracy of the LFIA test.FindingsThis study identified 485 eligible individuals and enrolled 460 participants. Baseline and 21-days follow-up seroprevalence were estimated at 52.0% (95% CI 44.9–59.0) and 56.7% (95% CI 48.2–65.3) with LFIA;and 80.7% (95% CI 74.1–87.3) and 81.1% (95% CI 74.4–87.8) with CLIA, with an overall IFR of 0.02%. There were 78.2% (95% CI 66.7–89.7) symptomatic individuals among the positive cases. Sensitivity and specificity of LFIA were estimated at 43.4% and 83.3% for IgM;46.5% and 91.5% for IgG;and 59.1% and 77.3% for combined tests.Originality/valueThe authors found high seroprevalence of anti-SARS-CoV-2 antibodies within the prison complex. The occurrence of asymptomatic infection highlights the importance of periodic mass testing in addition to case-finding of symptomatic individuals;however, the field performance of LFIA tests should be validated. This study recommends that vaccination strategies consider the inclusion of prisoners and prison staff in priority groups.
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Background: In the last two years the pandemic Coronavirus Disease 19 (Covid19), caused by the virus SARS-CoV- 2, described for the first time in Wuhan (China) at the end of 2019, has caused over 359 million cases of infections and 5 million deaths worldwide. To fight this emergency, the pursuit of science has focused on vaccines development against SARS-CoV- 2, including the vaccine BNT162b2. This vaccine contains mRNA translating for SARS-CoV- 2 spike protein wrapped in lipid nanoparticles and its use was approved at the end of 2020. It has been proved that both the BNT162b2 vaccine and the SARS-CoV- 2 infection result in the production of neutralizing antibodies but remains to be clarified the duration of these responses, also versus variants of concern. Method(s): The present study aimed to prospectively analyse and correlate the antibody response and the neutralization capability induced by vaccination with BNT162b2 in a cohort of Sardinian subjects, including a group previously Cov2 infected. Each participant was evaluated for serum SARS-CoV2 Ab IgG RDB, 7 (T1) and 30 (T2) days after the second inoculum of BNT162b2, with chemiluminescent immunoassays (CLIA) and microneutralization assay (MNA) determining the highest serum dilution protecting 90 % of the infected wells. Result(s): All the participants, with or without previous infection, developed a positive antibody response (IgG anti-RBD > 1 AU/ml) within 7 and 30 days from the second vaccine dose and a strong correlation was found between IgG antibody levels and neutralizing activity. A strong difference was observed between the antibody levels of the naive subjects and the ones previously infected, specifically the antibody levels were higher (both at T1 and T2) in the latter group. No significant antibody differences were found for gender and age groups. In addition, there were no significant differences in antibody titre between healthy and immune-mediated subjects. Conclusion(s): In conclusion, this study confirms observed differences in vaccine responses between infection-naive and subjects with history of natural infection, with the presence in the second group of a significantly higher neutralizing and anti-RBD antibody titer. It also demonstrates the strong correlation between anti-RBD antibody titre and neutralizing activity, without significant differences between healthy subjects and subjects with immuno-mediated disease in the short-term. Further follow-up is ongoing in this cohort.
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SARS-CoV-2-specific IgM antibodies wane during the first three months after infection and IgG antibody levels decline. This may limit the ability of antibody tests to identify previous SARS-CoV-2 infection at later time points. To examine if the diagnostic sensitivity of antibody tests falls off, we compared the sensitivity of two nucleoprotein-based antibody tests, the Roche Elecsis II Anti-SARS-CoV-2 and the Abbott SARS-CoV-2 IgG assay and three glycoprotein-based tests, the Abbott SARS-CoV-2 IgG II Quant, Siemens Atellica IM COV2T and Euroimmun SARS-CoV-2 assay with 53 sera obtained 6 months after SARS-CoV-2 infection. The sensitivity of the Roche, Abbott SARS-CoV-2 IgG II Quant and Siemens antibody assays was 94.3% (95% confidence interval (CI) 84.3-98.8%), 98.1 % (95% CI: 89.9-100%) and 100 % (95% CI: 93.3-100%). The sensitivity of the N-based Abbott SARS-CoV-2 IgG and the glycoprotein-based Euroimmun ELISA was 45.3 % (95% CI: 31.6-59.6%) and 83.3% (95% CI: 70.2-91.9%). The nucleoprotein-based Roche and the glycoprotein-based Abbott receptor binding domain (RBD) and Siemens tests were more sensitive than the N-based Abbott and the Euroimmun antibody tests (p = 0.0001 to p = 0.039). The N-based Abbott antibody test was less sensitive 6 months than 4-10 weeks after SARS-CoV-2 infection (p = 0.0001). The findings show that most SARS-CoV-2 antibody assays correctly identified previous infection 6 months after infection. The sensitivity of pan-Ig antibody tests was not reduced at 6 months when IgM antibodies have usually disappeared. However, one of the nucleoprotein-based antibody tests significantly lost diagnostic sensitivity over time.
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Objectives: Administration of the third dose of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine was initiated on December 1, 2021, in Japan. However, data on the long-term effects of this third vaccination remain scarce. Here, we examined the levels of SARS-CoV-2 antibodies in those who received the Pfizer BioNTech (BNT162b2) vaccine, 6 months after the third vaccination. Method(s): Samples from 40 healthy volunteers were used to measure SARS-CoV-2 antibodies with chemiluminescent assays against the receptor-binding domain (RBD) of the virus. Result(s): At 445 days after the first dose of BNT162b2, which is 180 days after the third vaccination, the mean anti-RBD IgG level was 159.4 AU/mL (SD 100.1 AU/mL), which was significantly higher than 144 days after the second vaccination, while mean anti-RBD IgM was baseline level (0.4 C.O.I.). The decline in IgG, 180 days after the third vaccination, was 74.1% (SD 16.1%), which was significantly lower than the 88.6% (SD 4.4%) decline observed 144 days after the second vaccination. Furthermore, we revealed that the reduction in IgG from 14 to 180 days after the third vaccination showed a significant inverse correlation with age, and the higher antibody response in younger participants at 14 days after the third vaccination disappeared at longer time points. Conclusion(s): The long-term durability of the IgG titer was significantly higher following the third vaccination compared with the second vaccination, and the reduction in IgG titer after the third vaccination inversely correlated with age.Copyright © 2022 the author(s), published by De Gruyter, Berlin/Boston.
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Rapid diagnosis of coronavirus disease 2019 (COVID-19)-infected patients is urgent in making decisions on public health measures. There are different types of diagnostic tests, such as quantitative PCR assay, antibody, and antigen-based and CRISPR-based tests, which detect genetic materials, viral proteins, or human antibodies in clinical samples. However, the proper test should be highly sensitive, quick, and affordable to address this life-threatening situation. This review article highlights the advantages and disadvantages of each test and compares its different features, such as sensitivity, specificity, and limit of detection to reach a reliable conclusion. Moreover, the FDA- authorized kits and studies' approaches toward these have been compared to provide a better perspective to the researchers.Copyright © 2022 Lippincott Williams and Wilkins. All rights reserved.
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Introduction: Immunoglobulin (Ig)G antibodies against SARS-CoV-2 are implicated in herd immunity. Humoral response to vaccines in kidney transplant recipients (KTRs) is documented to be sub-optimal. However, the response to non-messenger RNA(mRNA) based vaccines in KTRs is not known Methods: SARS-CoV-2 spike protein IgG antibody response was assessed in KTRs using chemiluminescence immunoassay. Patients were characterized by the number of vaccine doses received and Coronavirus disease 2019 (COVID-19) infection in past. Result(s): Out of 224 KTRs evaluated, 197 (87.94%) had positive S1/S2 IgG anti-SARS-CoV-2 antibodies with a median [IQR] titre of 307.5 AU/ml [91 AU/ml - 400 AU/ml]. High titres (in neutralizing range) were found in 170/224 (75.9%) KTRs. Seropositivity rates after 2 doses of vaccination were significantly higher than unvaccinated KTRs (88.67% vs 66.7%;p = 0.006). After adjusting for cofounders, KTRs with diabetes at the time of vaccination were less likely to develop antibody response (aOR 0.31, 95% confidence interval [CI] - 0.10, 0.90;p = 0.032). Higher eGFR was also an independent predictor of antibody response (aOR 1.04 95% CI - 1.01, 1.08;p = 0.005). KTRs vaccinated with CovishieldTM developed higher antibody response as compared to CovaxinTM (aOR 5.04, 95% CI - 1.56, 16.22;p = 0.007). Conclusion(s): A high rate of seroconversion was seen in KTRs after SARS-CoV-2 vaccination with non mRNA vaccines. The presence of diabetes and decreased eGFR independently predicted lower seroconversion rates. No conflict of interestCopyright © 2023
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In this paper, we present the first idea of using a DNA triple helix structure to inhibit CRISPR-Cas12a activity and apply it to the design of an electrochemiluminescent biosensor for the detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) gene in real samples and environmental surveillance. We employed a segment from the RdRp gene of SARS-CoV-2 by an entropy-driven reaction, which was paired with double-stranded DNA that can activate CRISPR-Cas12a activity by Hoogsteen pairing to form triple-stranded DNA, thereby inhibiting the binding interaction of the double-stranded DNA with CRISPR-Cas12a, which in turn inhibits the trans cleavage activity of CRISPR-Cas12a. The inhibited CRISPR-Cas12a is unable to cut the nucleic acid modified on the electrode surface, resulting in the inability of the ferrocene (Fc) modified on the other end of the nucleic acid to move away from the electrode surface, and thus failing to cause electrochemiluminescence changes in GOAu-Ru modified on the electrode surface. The extent of the electrogenic chemiluminescence change can reflect the concentration of the gene to be tested. Using this system, we achieved the detection of the SARS-CoV-2 RdRp gene with a detection limit of 32.80 aM.
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Vitamin D, a fat-soluble vitamin helps the body to absorb and retain calcium and phosphorus.Apart from this primary activity, it exhibits potent antimicrobial and antiinflammatory effects viaimmune-modulatory properties. Vitamin D has shown inhibitory effects on the production of pro-inflammatory cytokines, including TNF-alpha and IL- 6, by various mechanisms, includingdown-regulating viralinduced NFkB activation So, this present study aimed to study the relations of serum calcium, phosphorus and Vitamin D levels in association with severity and mortality in SARSCoV- 2 patients. A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate and severe) and outcome (discharged or deceased). Serum Ca, Po4, and ALP were analysed by the direct colourimetric method. Vitamin D was measured using the chemiluminescent immunoassay (CLIA). The median serum calcium, Phosphorus, ALP and vitamin D levels in COVID 19 patients were 8.02 mgldL (IQR, 7.24-8.71), 3.93 mgldL (IQR, 2.97- 4.36), 115 IU/L(IQR, 94-146) and 17.2 ng/mL (IQR, 11.6- 25.9) respectively. On comparing the different severity groups a significant difference was found in Vitamin D (p<0.002), ALP (p<0.00001) and calcium (p<0.0001). The serum calcium levels were significantly positively correlated with Vitamin D levels and negative correlation with the inflammatory markers like IL-6. Similarly, patients with low calcium and vitamin D were found to have a fatal outcome. 838 The multivariable analysis showed that a combination of low calcium and vitamin D with higher age are associated with mortality in COVID-19 patients. Serum calcium and Vitamin D were associated with the clinical severity and prognosis of patients with COVID-19.
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Background. Since the start of the COVID-19 pandemic, Chad has had 7,417 confirmed cases and 193 deaths, one of the lowest in Africa. Objective. This study assessed SARS-CoV-2 immunity in N'Djamena. Methods. In August-October 2021, eleven N'Djamena hospitals col-lected outpatient data and samples. IgG antibodies against SARS-CoV-2 nucleocapsid protein were identified using ELISA. "Bambino Gesu" Laboratory, Rome, Italy, performed external quality control with chemiluminescence assay. Results. 25-34-year-old (35.2%) made up the largest age group at 31.9+/-12.6 years. 56.4% were women, 1.3 women/men. The 7th district had 22.5% and the 1st 22.3%. Housewives and students dominated. Overall seroprevalence was 69.5% (95% CI: 67.7-71.3), females 68.2% (65.8-70.5) and males 71.2% (68.6-73.8). >44-year-old had 73.9% seroprevalence. Under-15s were 57.4% positive. Housewives (70.9%), civil servants (71.5%), and health workers (9.7%) had the highest antibody positivity. N'Djamena's 9th district had 73.1% optimism and the 3rd district had 52.5%. Seroprevalences were highest at Good Samaritan Hospital (75.4%) and National General Referral Hospital (74.7%). Conclusion. Our findings indicate a high circulation of SARS-CoV-2 in N'Djamena, despite low mortality and morbidity after the first two COVID-19 pandemic waves. This high seroprevalence must be considered in Chad's vaccine policy.Copyright © 2022 The Authors and PAGEPRESS PUBLICATIONS.