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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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Introduction: Generating adequate cellular and humoral responses are essential principle of vaccination. Immune system of renal transplant recipient remained compromised and speculated to less likely to develop antibody after vaccination. SARS-CoV-2 neutralizing antibody after anti-SARS-CoV-2 vaccination is required for the protection from subsequent viral infection. During COVID-19 disease, anti-SARS-CoV-2 specific antibody formation was correlated with the inflammatory cytokines level. Although, there is limited informations about serum cytokines and antibody formation after COVAXINTM, COVISHIELDTM vaccination in RTRs. Therefore, in the current study, we have evaluated the inflammatory cytokines response and anti-SARS-CoV-2 specific antibody formation in renal transplant recipient. Method(s): In this study, we have recruited 171 live-related renal transplant recipients vaccinated with two doses of either COVAXINTM (whole inactivated virus-based vaccine) or COVISHIELDTM (Simian adenovirus containing full-length spike protein-based vaccine). A 5 ml blood sample was collected after two weeks of 2nd dose of vaccination. The serum was separated and stored at -200C till the analysis. Anti-SARS-CoV-2 spike protein-specific IgG antibody titer was determined by chemiluminescent microparticle immunoassay methods and Cytokines IL-10, TGF-beta, IFN-gamma, IL-6 were measured by the ELISA techniques. Result(s): The overall anti-SARS-CoV-2 spike protein specific seroconversion after vaccination was observed in 149/171(87.13%) of RTRs with median IgG titer in seroconversion group 1191.90 (IQR, 398.70-2652.45) au/ml. The median and interquartile serum cytokines IL-10 level in seroconversion (n=149) vs non-seroconversion (n=22) group was 88.89 (IQR, 55.5-125.92) vs 92.59 (IQR, 48.14-148.14) pg/ml. The median TGF-beta level in seroconversion vs non-seroconversion group was 692.10 (IQR, 446.05-927.63) vs 1001.31 (IQR, 813.15-1125.65) pg/ml. The median IL-6 level in seroconversion vs non-seroconversion group was 46.66 (33.3-66.66) vs 28.33 (16.66-34.16) pg/ml. The median IFN-gamma level in seroconversion vs non-seroconversion group was 98.0 (IQR, 57.40-111.60) vs 50.0 (IQR, 30.55-52.55) pg/ml. The cytokines IL-6 and IFN-gamma level was positively correlated with anti-SARS-CoV-2 specific protein antibody titer (r=0.192;p=0.012), IFN-gamma (r=0.188;p=0.014). TGF-beta and IL-10 were negatively correlated with anti-SARS-CoV-2 specific protein antibody titer. For IL-10 (r=-0.065;p=0.39), for TGF-beta (r=-0.246;p=0.002). Further IFN-gamma was negatively correlated with TGF-beta (r=-0.268;p<0.001). Conclusion(s): Higher pro-inflammatory cytokines (IL-6, IFN-gamma) levels were associated with anti-SARS-CoV-2 spike protein-specific seroconversion, whereas higher anti-inflammatory cytokines IL-10 and TGF-beta were negatively associated with seroconversion after vaccination in renal transplant recipients. No conflict of interestCopyright © 2023
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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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BACKGROUND: Since pregnancy increases the risk of coronavirus disease 2019 (COVID-19) and its morbidity in pregnant women, it is necessary and recommended to prevent COVID-19 in pregnant women by vaccination such as by messenger RNA (mRNA) and inactivated vaccines. SARS-CoV-2 antibodies produced from vaccination have different results according to the type of vaccine given. The previous studies showed that IgG SARS-CoV-2 antibody levels were influenced by various factors such as gestational weeks at the time when vaccines were given. Moreover, there have been no previous studies on the effect of gestational age on quantitative IgG levels after the second dose of the vaccine especially in Indonesia during this pandemic due to some restrictions on daily activities. AIM: The aim of this study is to see the effect of giving the COVID-19 vaccine based on maternal gestational age (in trimester units) on maternal immunity (IgG SARS-CoV-2) in Dr. Hasan Sadikin General Hospital Bandung, Bandung Kiwari Hospital and Dr. Slamet Hospital, Garut. METHOD(S): This was a retrospective and cohort study by taking secondary data using consecutive sampling from the previous tests on the levels of SARS-CoV-2 IgG antibodies after two doses of inactivated vaccine and mRNA. Healthy pregnant women 14-34 weeks at the Department of Obstetrics and Gynecology, Dr. Hasan Sadikin (RSHS) Bandung, Bandung Kiwari Hospital, and Dr. Slamet Hospital for the period October 2021 to January 2022 were the target population of this study. Based on inclusion and exclusion criteria, 103 samples met the criteria. Examination of Maternal SARS-CoV-2 IgG Antibody Levels procedures was carried out using Chemiluminescent Microparticle Immunoassay. Statistical analysis was done using IBM SPSS 28.00 and p < 0.05 was considered statistically significant. RESULT(S): There was no significant difference (p = 0.236, p > 0.05) between the mean maternal age in the mRNA and inactivated vaccine groups. The mRNA and inactivated vaccine groups also had no significant difference in the gestational age category (0.70). There was a significant difference (p = 0.0001) between the levels of SARS-CoV-2 IgG antibodies after the vaccine in the mRNA and inactivated vaccine groups. There was no significant difference in the levels of SARS-CoV-2 IgG antibodies in the gestational age group after the mRNA vaccine (p = 0.426) and after the inactivated vaccine (p = 0.293). There was a significant difference (p < 0.05) in the subgroup analysis in each gestational age group (second trimester and third trimester) between SARS-CoV-2 IgG antibody levels after the mRNA vaccine compared to inactivated vaccine. DISCUSSIONS: The mRNA vaccine is based on the principle that mRNA is an intermediate messenger to be translated to an antigen after delivery to the host cell via various routes. However, inactivated vaccines contain viruses whose genetic material has been destroyed by heat, chemicals, or radiation, so they cannot infect cells and replicate but can still trigger an immune response. The administration of the vaccine in the second and third trimesters of pregnancy has the same results in increasing levels of SARS-CoV-2 IgG antibodies after mRNA and inactivated vaccination in this study. CONCLUSION(S): mRNA vaccination in pregnant women is better than inactivated vaccines based on the levels of IgG SARS-CoV-2 antibodies after vaccination. The maternal trimester of pregnancy was not a factor influencing the levels of SARS-CoV-2 IgG antibodies after either mRNA or inactivated COVID-19 vaccinations in this study.Copyright © 2023 Anita Deborah Anwar, Putri Nadhira Adinda Adriansyah, Ivan Christian Channel, Annisa Dewi Nugrahani, Febriani Febriani, Asep Surachman, Dhanny Primantara Johari Santoso, Akhmad Yogi Pramatirta, Budi Handono.
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The development of COVID-globulin, a COVID-19-specific human immunoglobulin preparation, involved choosing a method to quantify antibodies to SARS-CoV-2. Antibody titre determination by virus neutralisation (VN) is labour-intensive and unsuitable for large-scale application. To enable routine testing, it was necessary to develop a less demanding method;the enzyme-linked immunosorbent assay (ELISA) was the most appropriate of solutions. The lack of international and industry reference standards (RS) prompted the preparation and certification of an RS for COVID-globulin potency control. The aim of the study was to examine the possibility of substituting ELISA for VN and to develop an RS for SARS-CoV-2 antibody quantification in immunoglobulin preparations. Material(s) and Method(s): the authors used commercial ELISA kits by several manufacturers, COVID-globulin by Microgen (48 batches), and human plasma samples from multiple sources (1499 samples). The tests were performed by VN, ELISA, and chemiluminescent microparticle immunoassay. Result(s): the authors validated an ELISA method for SARSCoV-2 antibody quantification with the selected reagent kits by the National Medical Research Center for Hematology (NMRC for Hematology) and Euroimmun AG. The authors demonstrated the possibility of using ELISA instead of VN (with a correlation coefficient of more than 0.9). They developed and characterised an in-house RS for SARS-CoV-2 antibody content in human immunoglobulin preparations. The RS was certified in newly introduced anti-COVID units (ACU) and in international binding antibody units (BAU) using the World Health Organisation (WHO) international reference panel (NIBSC code: 20/268). The RS's potency was measured in terms of its neutralising activity in ACU (320 ACU/mL) and BAU (2234.8 BAU/mL). The authors established the relationship between ACU and BAU units. For the selected ELISA reagent kits, the conversion factors were 6.4 (NMRC for Hematology) and 7.0 (Euroimmun AG). Conclusion(s): the ELISA method for SARS-CoV-2 antibody quantification and the RS for SARS-CoV-2 antibody content can be applied to determine the potency of human anti-COVID-19 immunoglobulins.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.
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The development of COVID-globulin, a COVID-19-specific human immunoglobulin preparation, involved choosing a method to quantify antibodies to SARS-CoV-2. Antibody titre determination by virus neutralisation (VN) is labour-intensive and unsuitable for large-scale application. To enable routine testing, it was necessary to develop a less demanding method;the enzyme-linked immunosorbent assay (ELISA) was the most appropriate of solutions. The lack of international and industry reference standards (RS) prompted the preparation and certification of an RS for COVID-globulin potency control. The aim of the study was to examine the possibility of substituting ELISA for VN and to develop an RS for SARS-CoV-2 antibody quantification in immunoglobulin preparations. Materials and methods: the authors used commercial ELISA kits by several manufacturers, COVID-globulin by Microgen (48 batches), and human plasma samples from multiple sources (1499 samples). The tests were performed by VN, ELISA, and chemiluminescent microparticle immunoassay. Results: the authors validated an ELISA method for SARSCoV-2 antibody quantification with the selected reagent kits by the National Medical Research Center for Hematology (NMRC for Hematology) and Euroimmun AG. The authors demonstrated the possibility of using ELISA instead of VN (with a correlation coefficient of more than 0.9). They developed and characterised an in-house RS for SARS-CoV-2 antibody content in human immunoglobulin preparations. The RS was certified in newly introduced anti-COVID units (ACU) and in international binding antibody units (BAU) using the World Health Organisation (WHO) international reference panel (NIBSC code: 20/268). The RS's potency was measured in terms of its neutralising activity in ACU (320 ACU/mL) and BAU (2234.8 BAU/mL). The authors established the relationship between ACU and BAU units. For the selected ELISA reagent kits, the conversion factors were 6.4 (NMRC for Hematology) and 7.0 (Euroimmun AG). Conclusions: the ELISA method for SARS-CoV-2 antibody quantification and the RS for SARS-CoV-2 antibody content can be applied to determine the potency of human anti-COVID-19 immunoglobulins.
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Cellular and humoral responses are required for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) eradication. Antigen-presenting cells load SARS-CoV-2 peptides on human leukocyte antigen (HLA) with different avidities and present to T- and B-cells for imposing humoral and cellular responses. Due to immunosuppression, renal transplant recipient (RTR) patients are speculated to poorly form the antibody against the SARS-CoV-2. Therefore, determining the association of specific HLA alleles with anti-SARS-CoV-2 spike protein antibody formation will be helpful in managing the RTR having specific HLA alleles from SARS-CoV-2 infection and vaccination. Material(s) and Method(s): In this study, anti-SARS-CoV-2 spike protein antibody in 161 RTRs was determined by the chemiluminescent microparticle immunoassay methods, and HLA alleles were determined by the polymerase chain reaction-single-strand oligonucleotide methods and analyzed to study the HLA allele association with anti-SARS-CoV-2 spike protein-specific humoral response and severity of COVID-19 symptoms in recently SARS-CoV-2-infected RTRs. Result(s): The anti-SARS-CoV-2 spike protein specific antibody seroconversion rate in RTRs was 90.06% with a median titer of 751.80 AU/ml. The HLA class I alleles, A*11 in 22.1%, A*24 in 21.37%, A*33 in 20.68%, HLA B*15 in 11%, B*07 in 8.27%, HLA-C*30 in 20.93%, C*70 in 23.25% and HLA Class II alleles, DRB1*07 in 18.62%, DRB1*04 in 13.8%, HLA-DRB1*10 in 14.48%, HLA-DQA1*50 in 32.55% of RTRs were associated with the seroconversion. The mean SARS-CoV-2 clearance time was 18.25 +/- 8.14 days. Conclusion(s): RTRs with SARS-CoV-2 infection developed a robust seroconversion rate of 90.0% and different alleles of HLA-B, DRB1, and DQA1 were significantly associated with the seroconversion. Copyright © 2022 Indian Journal of Transplantation.
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BACKGROUND: Chronic Kidney Disease (CKD) Stage V patients on hemodialysis are a vulnerable group who have reported high rates of morbidity and mortality with Covid-19 infection. Covid-19 vaccination has been reported to be immunoprotective, and these patients are prioritized for Covid-19 vaccination. It is reported that dialysis patients develop lower seroconversion to vaccines. Indeed, this lower postvaccine response led to the adaptation of hepatitis B and influenza immunization schedules. Data are lacking on the humoral immune response to indigenously manufactured BBV152 (inactive) vaccine. In this study, we estimate the serologic response to BBV152 vaccine in hemodialysis patients in our Nephrology unit AIM OF THE STUDY: 1. To estimate the humoral immune response (conversion from seronegative to seropositive state) to inactivated SARS CoV2 vaccine administered as per The Government of India protocol in CKD stage V patients on maintenance HD 2. To correlate demographic clinical and biochemical/hematologic parameters with the humoral response METHODS: This study was a cross-sectional observational study conducted between September 2021 and March 2022 at the Department of Nephrology Tirunelveli Medical College Hospital. Ethics Committee approval was obtained. All CKD V patients on maintenance HD for at least three months who were willing to take BBV152 vaccine were enrolled in the study. Patients suffering from intercurrent illness those who had a prior PCR confirmed diagnosis of Covid-19, and patients who had positive baseline antibody titers were excluded from the study. Sample size was calculated according to the standard sample size calculator for observational study with a qualitative variable which computed a minimum sample size of 82. Detailed history taking clinical examination hematological and biochemical investigations assessment of nutritional status was performed as per structured questionnaire. For each patient, the following parameters were noted: Age, gender, BMI, native kidney disease comorbidities whether on immunosuppressant drugs, Hb absolute lymphocyte count, ESR serum albumin, and adequacy of dialysis by calculating spKt/V. Patients were then administered two doses of COVAXIN. Antibody titers were measured at baseline and four weeks after the first and second dose. Anti-SARS-CoV-2 IgG antibodies were measured using Access 2 Immunoassay System - Beckman Coulter by Chemiluminescence Microparticle Immunoassay which detects neutralizing antibodies against Receptor-Binding Domain of spike protein with a high sensitivity and specificity. The result of antibody titer was reported as nonreactive or reactive based on S/CO (Signal/Cut-Off ratio). S/CO 0.8 was nonreactive and S/CO 1 was reactive. Data was collected in MS-Excel, and IBM SPSSv26.0 was used for statistical analysis. RESULT(S): A total of 119 patients were enrolled out of which 107 patients completed the study. 75.7% (81 out of 107) patients achieved seroconversion after two doses of BBV152 which is lesser than seen in healthy controls. The rate of seroconversion was 66.4% after the first dose. Analysis of factors associated with poor seroconversion in this study showed increasing age, presence of diabetes, atherosclerotic cardiovascular disease, severe anemia, higher ESR, and severe hypoalbuminemia (Serum albumin < 2.5 g/dl) to be statistically significant. Patients who had lower BMI and spKt/V >1.2 showed a better seropositivity response in this study. HD vintage and absolute lymphocyte counts were not significantly associated with serologic response. Poor seroconversion is generally associated with immunosuppressant therapy, but this was not seen in our study which could be due to the small number (4 patients) in the study. Unique association of diabetes and severe anaemia with poor seroconversion was noted in this study CONCLUSION(S): 75.7% patients on maintenance hemodialysis achieved seroconversion after two doses of inactivated SARS CoV2 BBV152 vaccine. Increasing age, presence of diabetes, atherosclerotic cardiovascular disease, ana mia, inadequate hemodialysis, and hypoalbuminemia were associated with a lesser antibody response to the vaccine in this study. Revising future vaccine strategies with an aim at improving immunologic response in patients on hemodialysis with high-risk factors like diabetes mellitus brought out in our study could prove worthwhile.
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BACKGROUND: Coronavirus disease 2019 (COVID-19) has had a major effect on kidney and other solid organ transplant recipients. Vaccination has emerged as a key tool for controlling the pandemic. Kidney transplant recipients (KTR) are highly vulnerable to the serious complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and thus stand to benefit from vaccination. Various studies reported varying responses to different COVID vaccines;however, most data is available for SARS-CoV-2 messenger RNA (mRNA) as compared to other vaccines. This study aims to assess the humoral immune response to replication defective viral vectors [ChAdOx1-nCOV (Covishield)] and whole inactivated one [BBV-152 (Covaxin)] that are currently being administered in India in post-renal transplant patients after the first and second dose. AIM OF THE STUDY: Primary: To study antibody response after ChAdOx1-nCOV (Covishield) and BBV-152 (Covaxin) in post-renal transplant recipients Secondary: To study occurrence of adverse events related to COVID vaccine within one week of vaccination METHODS: Anti-SARS-CoV-2 anti-spike antibody titers were measured in 285 KTR recipients at baseline prior to vaccination and then 3 weeks +/- 3 days after first dose and 3 weeks +/- 3 days after second dose of ChAdOx1-nCOV (Covishield) (n = 232) and BBV-152 (Covaxin) (n = 55) vaccine. Immune response was defined as seropositivity to the anti-spike antibody by chemiluminescence immunoassay method and chemiluminescent microparticle immunoassay. Primary outcome was seroconversion after two doses of COVAXIN TM and COVISHIELD TM. The secondary outcome studied was the occurrence of adverse events related to the COVID vaccine within one week of vaccination. Patients with a history of symptomatic COVID-19 infections were excluded from the study. RESULT(S): At baseline, 18 (33.3%) and 70 (30.3%) of KTRs were found to be seropositive before receiving COVAXIN TM and COVISHIELD TM vaccination respectively despite giving no history of previous symptomatic COVID-19 infection. After first dose of COVAXIN TM and COVISHIELD TM vaccination, 42 (77.8%) and 182 (78.8%) were found to be seropositive and after second dose 43 (79.6%) and 183 (79.2%) were seropositive respectively. Seroconversion was found in 81.2% of males compared to 66.7% of females after the first dose of Covid vaccine which was statistically significant (p = 0.022). Seroconversion rate in -50 years was 76.7% (232/285) and >50 years was 90.6% (53/285) (p = 0.025). Seroconversion was not statistically different in KTR whether they were ABO compatible or incompatible, type of induction agent or maintenance immunosuppression used. Common adverse effects encountered were fever, myalgia, headache which settled in 1-2 days. There was no episode of acute rejection reported after the COVID vaccine. CONCLUSION(S): Both ChAdOx1-nCOV (Covishield) and BBV- 152 (Covaxin) were well tolerated and induced robust antibody formation in KTRs in the Indian population.
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BACKGROUND: Cellular and humoral response are required for SARS-CoV-2 eradication. Antigen-presenting cell loads SARS-CoV-2 peptides on human leukocyte antigen with different avidity and present to T and B cell for humoral and cellular activity. Due to immunosuppression, renal transplant recipient patients are speculated to poorly form the antibody against SARS-CoV-2 virus. Therefore, determining the association of specific HLA alleles with anti-SARS-CoV-2 spike protein antibody formation will be helpful in managing the renal transplant recipient patients having specific HLA alleles from SARS-CoV-2 infection and vaccination. AIM OF THE STUDY: To study the association of human leukocyte antigens with anti-SARS-CoV-2 spike protein antibody formation in response to vaccination in renal allograft recipient METHODS: In this study, anti-SARS-CoV-2 spike protein antibody in 78 renal allograft recipient patients were determined by the chemiluminescent microparticle immunoassay methods and human leukocyte antigen alleles were determined by the polymerase chain reaction-single strand oligonucleotide methods and analyzed to study the association of human leukocyte antigens with anti-SARS-CoV-2 spike protein antibody formation in response to vaccination in renal allograft recipient RESULTS: The mean age of the patients in seroconversion vs non-seroconversion (45.88 +/- 8.86 vs 45.55 +/- 8.74, p value - 0.90). The post-transplant interval in seroconversion vs non-seroconversion (103.63 +/- 57.57 vs 77.45 +/- 35.25, p value - 0.14). The duration between the vaccination with both the doses and sample collection of renal transplant recipients in seroconversion vs non- seroconversion (47.58 +/- 30.18 vs 45.55 +/- 35, p value - 0.85). The anti-SARS-CoV-2 spike protein antibody seroconversion rate in renal allograft recipients were 85.9% with median titer in seroconversion vs non- seroconversion 3175.00 (IQR, 798.50 - 8391.70) vs 5.50 (IQR, 4.10 - 8.20, p value - 0.001). In covishield vs covaxin group 2500.70 (IQR, 146.40 - 7705.60) vs 1828.70 (IQR, 665.00 - 3765.10, p value - 0.63). The frequency of HLA class I alleles A*26 was 18.18%, B*08 was 18.18%, C*05 was 25% and Class II HLA alleles - DRB1*03 was 18.18%, and HLADQA1* 20 was 25% of patient were significantly associated with non-seroconversion and C*06 was 18.75% were significantly associated with seroconversion. CONCLUSION(S): Renal transplant recipients with anti-SARSCoV- 2 vaccination developed a robust seroconversion rate of 85.9% and alleles of A*26, B*08, C*05, DRB1*03, and DQA1*20 were significantly associated with non-seroconversion.
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Introduction: Some disease modifying treatments (DMTs) impair response to SARS-CoV-2 vaccines in multiple sclerosis (MS), potentially increasing the risk of breakthrough infections. Objective(s): To investigate longitudinal post-vaccine antibody dynamics and memory B cell responses after 2 and 3 SARSCoV- 2 mRNA vaccine doses, and their association with risk of COVID-19 in MS patients treated with different DMTs. Method(s): Prospective observational monocenter cohort study in MS patients undergoing SARS-CoV-2 mRNA vaccinations. Anti- SARS-CoV-2 spike IgG serum titers were measured by chemiluminescence microparticle immunoassay. Frequency of spike-specific memory B cells were measured upon polyclonal stimulation of total PBMCs and screening of secreted antibodies by ELISA. Result(s): We recruited 120 MS patients (58 on anti-CD20, 9 on S1P-modulators, 15 on cladribine, 24 on teriflunomide and 14 untreated) and collected 392 samples before and up to 10.8 months after a 2nd vaccine dose. Compared to no treatment, anti-CD20 antibodies (beta=-2.07, p<0.001) and S1P-modulators (beta=-2.02, p<0.001) were associated with lower anti-spike IgG titers, while teriflunomide and cladribine were not. Anti-spike IgG titers progressively decreased with months since last vaccine dose (beta=-0.14, p<0.001), independently of DMTs. Within anti-CD20 treated patients, anti-spike IgG remained constantly higher in those with greater baseline CD19+ B cell counts and were not influenced by post-vaccine anti-CD20 infusions. Antispike IgG titers increased after a 3rd vaccine dose on cladribine and teriflunomide and marginally on anti-CD20 and S1Pmodulators. Spike-specific memory B cell responses were weaker on S1P-modulators and anti-CD20 than on teriflunomide and influenced by post-vaccine anti-CD20 infusions. Risk of SARS-CoV-2 infection was predicted by SARS-CoV-2 IgG at last sample before infection (OR=0.56, 95%CI=0.37-0.86, p=0.008). Conclusion(s): Post-vaccine SARS-CoV-2 IgG antibody titers progressively decrease over time in MS regardless of DMTs, and are associated with risk of breakthrough COVID-19. Both immediate humoral and specific memory B cell responses are diminished in patients on S1P-modulator and anti-CD20 antibody treatments. Within the latter group, B cell count at first vaccine dose determines anti-spike IgG production shortly after vaccination, whereas post-vaccine anti-CD20 infusions negatively impact memory B cell responses.
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Introduction: Patients with Inflammatory Bowel Disease (IBD) frequently receive immunomodulating treatment, which may render them at increased risk of an attenuated immune response upon vaccination. In this study, we assessed the effects of different types of commonly prescribed immunosuppressive medications on the serological response after vaccination against SARS-CoV-2 in patients with IBD. Aims & Methods: In this prospective observational cohort study, IgG antibody titers against SARS-CoV-2 were measured 2-10 weeks after completion of standard vaccination regimens in patients with IBD. Clinical characteristics, previous history of SARS-CoV-2 infection, type of vaccine (mRNA- or vector-based) and medication use were recorded at the time of sampling. Subsequently, a chemiluminescent microparticle immunoassay was used for the quantitative determination of IgG antibodies against the receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2. Result(s): Three hundred and twelve (312) patients with IBD were included (172 Crohn's disease [CD] and 140 ulcerative colitis [UC]). Seroconversion (defined as titer of >50 AU/ml) was achieved in 98.3% of patients. Antibody concentrations were significantly lower in patients treated with TNF-alpha-antagonists vs. non-users of TNF-alpha-antagonists (geometric mean [95% confidence interval]: 2204 [1655-2935] vs. 5002 [4089-6116] AU/ml, P<0.001). In multivariable models, use of TNF-alpha-antagonists (P<0.001), vector vaccines (P<0.001), age (>50 years) (P<0.01) and CD (P<0.05) were independently associated with lower anti-SARS-CoV-2 antibody titers. In patients who received mRNA vaccines, users of thiopurines (either prescribed as monotherapy or in combination with biologicals) demonstrated significantly lower antibody titers compared to those who were thiopurine non-users (P<0.05). Conclusion(s): Despite reassuring findings that most patients with IBD have detectable antibodies after anti-SARS-CoV-2 vaccination, TNF-alpha- antagonists were found to be strongly associated with an attenuated IgG antibody response after vaccination against SARS-CoV-2, independent of vaccine type, the time elapsed after vaccination and blood sampling, prior SARS-CoV-2 infection and patient age. Patients treated with thiopurines and receiving mRNA-based vaccines demonstrated lower anti-SARS-CoV-2 antibody titers compared with non-users. This specific subgroup of patients treated with TNF-alpha-antagonists may benefit from active booster vaccine prioritization, preferably with mRNA-based vaccines.
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Objectives. A variety of different anti-SARS-CoV-2 IgG antibody tests are already available in medical laboratories worldwide, and it is quite difficult to compare obtained results due to the diversity and lack of standardization. METHODS. The study included 16 serum samples of patients vaccinated against COVID-19 with different kinds of vaccines and their combinations. Two commonly used anti-SARS-CoV-2 IgG spike protein antibody quantitative assays (Abbott Chemiluminescent Microparticle Immunoassay (CMIA) and EUROIMMUN ELISA) were evaluated for correlation. RESULTS. SARS-CoV-2 IgG antibody results of Abbott CMIA and EUROIMMUN ELISA assays demonstrated a good correlation (r = 0.7902) between obtained results among patients. Only one sample showed discordant results, respectively;CMIA displayed positive (68 AU/mL;cut-off value is 50 AU/mL), but ELISA-a negative (0.7 ratio;cut-off value is 0.8 ratio) result. CONCLUSIONS. Anti-SARS-Cov-2 IgG spike protein antibody results correlate between Abbott CMIA and EUROIMMUN ELISA assay, despite the lack of standardization of these assays. However, more studies with a wider range of participants need to be carried out to fully demonstrate and prove this correlation, also considering each patient's history of vaccination against COVID-19 and possible COVID-19 infection in their medical history.
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Purpose: To evaluate the seroconversion rate in kidney transplant recipients (KTR), compared to two non-transplanted groups of patients, and identify predictors of seroconversion in COVID-19 convalescent patients. Method(s): A retrospective cohort study enrolled RT-PCR COVID-19 diagnosed patients (Mar/20 and Oct/2020) of three groups: 601 KTR, 211 health care workers (HCW), and 170 non-transplanted inhabitants (INH) in a countryside city in the state of Sao Paulo - Brazil. At least 14 days after diagnosis, all survivors underwent antibody testing by chemiluminescent microparticle immunoassay (titter expressed in RLU). The primary outcome was seroconversion. The group-adjusted multivariable model for the probability of seroconversion was built by generalized linear mixed models with binary logistic regression and the discrimination performance by AUC-ROC. Result(s): Several differences were observed among groups regarding demographic data and COVID-19 clinical presentation. Of note, KTR were older (54.0 years old vs. 37.0 in HCW vs. 42.0 in INH, P<0.001), more frequently had comorbidities (P<0.001), and severe COVID-19 (P<0.001). Compared to HCW and INH, respectively, admission to ICU (44.9% vs. 0% vs. 1.8%), MV requirement (32.3% vs. 0% vs. 1.8%), and death (28.8% vs. 0% vs. 1.2%) were significantly more frequent in KTR (P<0.001). On the other hand, the seroconversion rate was not different among survivors: 76.2% for KTR, 74.9% for HCW, and 82.2% for INH (P=0.35). The IgG anti-SARS-CoV-2 was slightly higher among INH: 5.8 RLU vs. 5.4 for KTR and 4.4 for HCW (P=0.009). Seroconversion was associated with a shorter time between infection and blood sample collection (OR for each day= 0.986;P<0.001) and increased by 64% if the fever was a COVID-19 symptom (OR=1.737;P=0.017), 78% if the cough was present (OR=1.785;P=0.005) and 98% if the ventilatory support was required (OR=1.981;P=0.017). This predictive model achieved an AU-ROC of 0.730 (P<0.001). Conclusion(s): As expected, the rates of clinical deterioration to ICU admission, MV requirement, and death were significantly higher among KTR. However, among the survivors, KTR had a similar rate of seroconversion, associated with clinical severity parameters and a shorter time of blood sample collection.
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Introduction/ Background: The World Health Organization reports that approximately 80% of COVID-19 infections seen in Africans were asymptomatic compared to 40% - 50% seen globally. Validated serological assays are thus critical in conducting reliable serosurveys;however most SARS-CoV-2 immunoassays were validated using specimens from China, Europe, or United States populations. Methods: The study evaluated performance of five commercial SARS-CoV-2 immunoassays to inform use in serosurveys in Nigeria. Four semi-quantitative ELISAs (Euroimmun Anti-SARS-CoV-2 NCP IgG, Euroimmun spike SARS-CoV-2 IgG, Omega Mologic COVID-19 IgG, Bio-Rad Platelia SARS-COV-2 Total Ab) and one chemiluminescent microparticle immunoassay (Abbott Architect SARS-COV-2 IgG) were assessed. The analytical performance characteristics was evaluated using plasma from 100 SARS-CoV-2 polymerase chain reaction (PCR)-positive patients from varied time points post-PCR confirmation and 100 pre-pandemic samples (50 HIV-positive and 50 hepatitis B-positive). Results: The Bio-Rad assay was evaluated, but failed manufacturer-specified validation steps. The Euroimmun NCP, Euroimmun spike, and Mologic assays had sensitivities of 73.7%, 74.4% and 76.9%, respectively, on samples taken 15-58 days after PCR confirmation, and specificities of 97%, 100%, and 83.8%, respectively. The Abbott assay had 71.3% sensitivity and 100% specificity on the same panel. Parallel or serial algorithms combining two of the above immunoassays did not substantially improve sensitivity or specificity. Impact: Validated assays are necessary in conducting reliable seroepidemiology surveys and in tracking asymptomatic infections. These findings highlight the importance of in-country validations of SARS-CoV-2 serological assays prior to use to ensure accurate results are available for public health decision making to control the COVID-19 pandemic in Africa. Conclusion: The study results showed lower sensitivity and, for one immunoassay, lower specificity, compared to manufacturers' results and other reported validations. Seroprevalence results using these assays might need to be interpreted with caution in Nigeria and similar settings.
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Objective(s): The aim of this study was to study the humoral immune response to SARS-CoV-2 following vaccination in MS patients. Material(s) and Method(s): We performed a prospective study including all MS patients receiving one of the approved COVID-19 vaccines since January to September 2021. Demographic characteristics, MS treatments and adverse events reports after COVID-19 vaccination of vaccinated MS patients were collected. We analyzed the antibody response to SARS-CoV-2 vaccines with a chemiluminescent microparticle immunoassay (CMIA) from Abbot in MS patients with different DMTs at week 3, week 6 and month 3 after the first dose. The positivity cutoff is ≥50 AU/ml (manufacturer defined). 200 Healthy healthcare professionals were the control group. Result(s): We analyzed 165 vaccinated MS patients: 106 with Pfizer, 14 with Moderna, 42 with both doses of Astra zeneca and 3 with Jannsen. The mean age of patients was 45 (range: 21-71) and 46 for the controls. The most frequent adverse events were pain at injection site, headache and fatigue for 24-48 hours. No differences between MS patients and controls. No increased risk of relapse was noted in the first six months. 120 patients have received both doses of mRNA vaccine. Overall, mean antibody titers response to SARS-CoV-2 SARS-CoV-2 at three weeks was 7910,3 AU/mL (range 0-74947), at 6 weeks 16347,9 UA/mL (range:0-52380,5) and at 3 months 8182,10 UA/ml (range:0-33752,4) in mRNA vaccinated patients. By the mRNA vaccinated control group mean antibody titers response to SARS-CoV-2 SARS-CoV-2 at three weeks was 9397 AU/mL and at 6 weeks 18120 UA/mL Performing a subanalysis of the different DMTs: Only 3 out of 20 patients treated with ocrelizumab developed antibodies. Six vaccinated patients treated with rituximab had no antibody response. Four from 16 patients treated with fingolimod failed to develop a post-vaccination humoral response (< 50 AU/ml). 4 of 5 patients treated with ofatumumab developed have an adequate humoral response. Patients treated with interferon Beta, glatiramer acetate, teriflunomide, dimethyl fumarate, vaccinated with mRNA vaccines developed a similar post vaccination humoral response than healthy controls. Conclusion(s): Most of MS treated patients developed enough antibodies to SARS-CoV-2. The adverse events on MS patients were similar to the general population. No increase of relapse activity was observed. Some patients treated with ocrelizumab, rituximab and fingolimod have no developed a humoral response to SARS-CoV-2 vaccination. Hence we conclude that all approved COVID-19 vaccines are safe in MS patients and effective in most patients. However vaccine strategy in patients treated with anti-CD20 and fingolimod need further studies.
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Background: Coronavirus disease (COVID-19), whose first victim was reported in December 2019 in China, has hit the whole of humankind's health as well as economy. The exact numbers of individuals, who have come into contact with this virus, cannot be estimated because most of the individuals are asymptomatic. The cases reported cannot estimate the accurate number of individuals who were infected with the SARSCoV- 2 virus. To keep an eye on such pandemic, seroprevalence studies can be a useful tool for assessing the extent of SARS-CoV-2 infected asymptomatic individuals. Limited work has been carried out and published in this field and this particular cohort in Pakistan, especially in Khyber Pakhtunkhwa. Therefore, this parameter was used in the healthy population of blood donors to assess the prevalence of COVID-19 disease during second and third waves in the province. Aims: To determine and compare the SARS-CoV-2 antibodies seroprevalence during second and third waves of COVID-19 in Khyber Pakhtunkhwa, Province of Pakistan. Methods: The descriptive cross-sectional study was conducted during the second and third waves of COVID-19, at Regional Blood Center (RBC) Peshawar, Pakistan. During the 2nd wave of Covid-19 (November 2020 to January 2020), 2100 samples were collected, while in the 3rd wave a total of 1900 samples were collected from healthy blood donors. After TTI's screening by CMIA technique using Abbott Architect i2000 SR, all the seronegative samples were then screened for the presence of SARS-CoV-2 antibodies using Electro Chemiluminescence immunoassay (ECLIA) technique, by Roche Cobas e-411 analyser. Cut off value of 0.99 was taken according to the kit manufacturer's recommendation. SPSS® version 24 was used for the statistical analysis. The Regional Blood Center Peshawar ethical committee endorsed the study. Results: During both the waves of COVID-19, 4000 healthy blood donors were screened. Age range was 18-60 years, with the mean age of 26.30 ± 7.05. Among the 2100 samples of the 2nd wave of COVID-19, 1176 (56%) were found positive for SARS-CoV-2 antibodies, while 1235 (65%) seropositivity was recorded among the 1900 samples collected during the 3rd wave of COVID-19. Summary/Conclusions: This study was conducted among the blood donors, who were found fit according to the WHO & National guidelines. The study findings showed an increase in the SARS-CoV-2 antibodies seroprevalence during second and third waves of COVID-19, indicating a positive sign towards achieving Herd immunity.
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BACKGROUND AND AIMS: The poor humoral response after vaccination against SARS-CoV-2 in kidney transplant (KT) patients led to the approval of a third dose. Recent data show an increase in the antibody titer, although lower than in the general population. Our aim is to analyze the humoral immune response after the third dose a mRNA vaccine against SARS-CoV-2 and the evolution of the antispike antibody (antiS) titers in KT recipients. METHOD: We performed a prospective cohort study of stable KT patients from our center who received three doses of a mRNA vaccine from March to November 2021. KT recipients with less than 6 months after transplantation and with active oncological or hematologic disease were excluded. We determined antiS titers (Abbott SARS-CoV- 2 IgG chemiluminescent microparticle immunoassay) at baseline, one month after the second dose and one month after the third one. We compared those KT patients who seroconverted with 2 and with 3 doses of vaccine and those who did not seroconvert. To identify risk factors for no seroconversion, a logistic regression analysis was carried out. RESULTS: We included 83 KT. Mean age was 59.3 years and 62.7% were male. The median time from KT to the first vaccine dose was 94 months and between the second and third dose median time was 4 months. Seroconversion rate was 63.8% after 2 doses and 85.5% after the third one (P < 0.001). Twelve KT did not develop antibodies (Table 1). Patients who did not seroconvert were older (P = 0.047), had a worse renal function (P = 0.009) and had fewer lymphocytes than those that developed antibodies (0.013). Besides, they almost half of them received a KT from a non-heart-beating donor (P = 0.026) and were treated with thymoglobulin in the 2 years prior to the vaccine more frequently (P = 0.007). In patients who seroconverted after 2 doses, we observed a 10-fold increase in the antiS titer after the third vaccine (82 [34-350] UI/mL versus 814 [205-2415] UI/mL;P < 0.001). No patients had neither acute rejection nor serious adverse effects. In the multivariable analysis advanced age, a worse kidney function and recent treatment with thymoglobulin were risk factors for no seroconversion (Table 1). CONCLUSION: The third dose of a mRNA vaccine against SARS-CoV-2 significantly increased the seroconversion rate and the antiS titers in stable KT patients. Advanced age, poorer kidney function and immunosuppressive treatment are risk factors for no seroconversion. (Table Presented).
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BACKGROUND AND AIMS: Patients (pts) with end-stage kidney disease (ESRD) may be more vulnerable to infections and may have a suboptimal response to vaccination. Dialysis patient (pt) began to be vaccinated against COVID-19 in February 2021. However, there were many doubts about whether immunization would be effective for them, as these pts have an impaired immune system, and it seems that this population responds poorly to vaccinations. Serum neutralizing antibodies (AbN) rapidly appear after the SARS-CoV-2 infection and the vaccination and are maintained for several months. The emergence of SARS-CoV-2 variants has raised concerns about the breadth of the neutralizing antibody responses. METHOD: Serum samples were obtained from 181 patients receiving dialysis. Levels of circulating SARS-CoV-2 anti-spike IgG(S) and anti-nucleocapsid IgG (N) antibodies were quantified using the Abbott Diagnostics SARS-CoV-2 IgG chemiluminescent microparticle immunoassay (Abbott Diagnostics, Abbott Park, IL, USA) on an Abbott Diagnostics Architect i2000 SR and an Alinity analyzer, according to the manufacturer's instructions. Serum neutralizing antibodies (AbN) by commercially available assays (cPass SARS-CoV-2 Neutralization Antibody Detection Kit), at the first and the third months after the vaccination, were identified. RESULTS: The IgG-spike Abs had a statistically significant decrease at 3 months after the vaccination in relation to the measurements 1 month after that. AbN had a statistically significant decline at 3 months after the vaccination in relation to the measurements 1 month after. Pts with cardiovascular disease (CD) had significantly lower levels of antibodies than those who did not have CD. Additionally, CD was an aggravating factor in combination with the other comorbidities for the development of antibodies. Pts with a history of malignancy had significantly lower levels of antibodies in relation to those who did not. Those under therapy with antihistamines in the 1st month after the vaccination presented a statistically lower level of the AbNs, but this difference did not exist in the measurements 3 months after vaccination. There was a correlation between the AbNs and the age, also between the time these patients underwent dialysis. Those who had COVID-19 infection presented higher levels of the antibodies AbN/IgG-spiked Ab at 3 months. CONCLUSION: It is presented that the IgG-spike Abs and the AbN had a statistically significant decrease at 3 months after the vaccination, which shows the importance of completing vaccination with the third dose after 3 months. Also, it is presented that CD is a risk factor for lower levels of Abs. Randomized clinical trials for COVID-19 vaccines included a few patients with kidney disease;therefore, the vaccine immunogenicity is uncertain in this population.
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BACKGROUND AND AIMS: SARS-CoV-2 represents a challenge for hemodialysis (HD) patients due to their diminished immune defenses in the setting of kidney disease, multiple comorbidities and older age. COVID-19 vaccines have brought hope but these patients' reduced response to immunization with the hepatitis B and influenza vaccination raised concerns about a lower efficacy of the new vaccines. This study aimed at quantifying IgG in sequential samples from HD patients and compare its titers with those of a non-HD healthy population, after vaccination. METHOD: We compared IgG titers using Abbott SARS-CoV-2 IgG II Quantitative Antibody Assay on the Alinity i system (Abbott Diagnostics, Chicago, US), 3-4 months after the Pfizer-BioNTech COVID-19 vaccine in 54 HD patients and 59 non-HD controls. This method is a two-step chemiluminescent microparticle immunoassay used for the quantitative determination of IgG antibodies to the receptor binding domain of the S1 subunit of the spike protein of SARS-CoV-2. HD patients performed their treatments at the HD unit of Felgueiras, a municipality in the district of Porto, Portugal, and were vaccinated in January/February 2021. The controls were healthcare workers from the hospital of Gaia. All HD patients received 2 vaccine doses even if they had previously had COVID-19 (N = 8) whereas controls only received 1 dose of the vaccine if they had been infected (N = 28). For 48 of the HD patients, we reassessed IgG levels 8 months after vaccination and compared it with the first measurements. Statistical analysis used SPSS ® . Parametric variables were described with mean ± standard deviation and compared using independent and paired-samples t-tests. Non parametric variables were described with median ± interquartile range (IQR) and compared using Mann-Whitney U and Wilcoxon tests. RESULTS: HD patients were older (67.6 ± 15.8 years of age) when compared to the healthy controls (42.4 ± 12.1 years of age). Only 1 HD patient had IgG below the positive cutoff after vaccination, all others seroconverted. Median values were significantly lower among HD patients compared to the controls (973 IQR 387-3306 versus 4809 IQR 2557-7746 AU/mL;p < 0.001). This difference remained significant even if those who had COVID-19 were removed from the analysis (p < 0.001). Those who had had COVID-19 before vaccination, showed significantly increased IgG levels compared to those who had not (6956 IQR 4810-13 101 versus 1520 IQR 554-3950 AU/mL;p < 0.001), a similar finding among HD and non-HD individuals. In HD patients for whom this data was available, IgG levels decayed from month 4 to month 8 (973 IQR 387-3306 versus 382 IQR 168-2071 AU/mL;p < 0.001). CONCLUSION: HD patients seem to have an impaired immune response after the COVID-19 vaccines, similar to what happens with vaccines against other viruses. After the Pfizer-BioNTech COVID-19 vaccine 98% of the patients seroconverted. Although they were older which may have played a role, a limitation to the analysis, IgG titers were lower in HD-patients than in the control group. Antibodies declined over the next months. This decline may be associated with loss of neutralizing antibodies, cellular responses to SARS-CoV-2 and risk of reinfection.