scholarly journals Humoral Responses to Single-Dose BNT162b2 mRNA Vaccination in Dialysis Patients Previously Infected With SARS-CoV-2

2021 ◽  
Vol 8 ◽  
Author(s):  
Claudius Speer ◽  
Christian Morath ◽  
Maximilian Töllner ◽  
Mirabel Buylaert ◽  
Daniel Göth ◽  
...  

Seroconversion rates following infection and vaccination are lower in dialysis patients compared to healthy controls. There is an urgent need for the characterization of humoral responses and success of a single-dose SARS-CoV-2 vaccination in previously infected dialysis patients. We performed a dual-center cohort study comparing three different groups: 25 unvaccinated hemodialysis patients after PCR-confirmed COVID-19 (Group 1), 43 hemodialysis patients after two-time BNT162b2 vaccination without prior SARS-CoV-2 infection (Group 2), and 13 single-dose vaccinated hemodialysis patients with prior SARS-CoV-2 infection (Group 3). Group 3 consists of seven patients from Group 1 and 6 additional patients with sera only available after single-dose vaccination. Anti-S1 IgG, neutralizing antibodies, and antibodies against various SARS-CoV-2 protein epitopes were measured 3 weeks after the first and 3 weeks after the second vaccination in patients without prior SARS-CoV-2 infection, 6 weeks after the onset of COVID-19 in unvaccinated patients, and 3 weeks after single-dose vaccination in patients with prior SARS-CoV-2 infection, respectively. Unvaccinated patients after COVID-19 showed a significantly higher neutralizing antibody capacity than two-time vaccinated patients without prior COVID-19 [median (IQR) percent inhibition 88.0 (71.5–95.5) vs. 50.7 (26.4–81.0); P = 0.018]. After one single vaccine dose, previously infected individuals generated 15- to 34-fold higher levels of anti-S1 IgG than age- and dialysis vintage-matched unvaccinated patients after infection or two-time vaccinated patients without prior SARS-CoV-2 infection with a median (IQR) index of 274 (151–791) compared to 18 (8–41) and 8 (1–21) (for both P < 0.001). With a median (IQR) percent inhibition of 97.6 (97.2–98.9), the neutralizing capacity of SARS-CoV-2 antibodies was significantly higher in single-dose vaccinated patients with prior SARS-CoV-2 infection compared to other groups (for both P < 0.01). Bead-based analysis showed high antibody reactivity against various SARS-CoV-2 spike protein epitopes after single-dose vaccination in previously infected patients. In conclusion, single-dose vaccination in previously infected dialysis patients induced a strong and broad antibody reactivity against various SARS-CoV-2 spike protein epitopes with high neutralizing capacity.

2021 ◽  
pp. 1-7
Author(s):  
Emre Erdem ◽  
Ahmet Karatas ◽  
Tevfik Ecder

<b><i>Introduction:</i></b> The effect of high serum ferritin levels on long-term mortality in hemodialysis patients is unknown. The relationship between serum ferritin levels and 5-year all-cause mortality in hemodialysis patients was investigated in this study. <b><i>Methods:</i></b> A total of 173 prevalent hemodialysis patients were included in this study. The patients were followed for up to 5 years and divided into 3 groups according to time-averaged serum ferritin levels (group 1: serum ferritin &#x3c;800 ng/mL, group 2: serum ferritin 800–1,500 ng/mL, and group 3: serum ferritin &#x3e;1,500 ng/mL). Along with the serum ferritin levels, other clinical and laboratory variables that may affect mortality were also included in the Cox proportional-hazards regression analysis. <b><i>Results:</i></b> Eighty-one (47%) patients died during the 5-year follow-up period. The median follow-up time was 38 (17.5–60) months. The 5-year survival rates of groups 1, 2, and 3 were 44, 64, and 27%, respectively. In group 3, the survival was lower than in groups 1 and 2 (log-rank test, <i>p</i> = 0.002). In group 1, the mortality was significantly lower than in group 3 (HR [95% CI]: 0.16 [0.05–0.49]; <i>p</i> = 0.001). In group 2, the mortality was also lower than in group 3 (HR [95% CI]: 0.32 [0.12–0.88]; <i>p</i> = 0.026). No significant difference in mortality between groups 1 and 2 was found (HR [95% CI]: 0.49 [0.23–1.04]; <i>p</i> = 0.063). <b><i>Conclusion:</i></b> Time-averaged serum ferritin levels &#x3e;1,500 ng/mL in hemodialysis patients are associated with an increased 5-year all-cause mortality risk.


2002 ◽  
Vol 13 (2) ◽  
pp. 519-527
Author(s):  
Igor A. Laskowski ◽  
Johann Pratschke ◽  
Markus J. Wilhelm ◽  
Victor M. Dong ◽  
Francisca Beato ◽  
...  

ABSTRACT. The effects of a signaling anti-CD28 mAb (JJ319), which interferes with the CD28-B7 T cell costimulation pathway thought to be involved in the development of chronic rejection of organ transplants, was investigated. Functional, morphologic, and molecular changes in rat renal allografts were examined up to 24 wk after placement. Control Lewis rats, recipients of F344 kidneys, received a single dose of a nonspecific mouse mAb intravenously on the day of transplantation (group 1). Group 2 animals were given anti-CD28 mAb in similar fashion. Group 3 animals were treated with a short course of cyclosporin A (CsA), and group 4 received both anti-CD 28 mAb and CsA. The majority (>95%) of animals in groups 2, 3, and 4 survived throughout the follow-up, compared with 28% in group 1 (P < 0.001). Group 2 and 4 recipients produced negligible proteinuria, whereas group 1 controls developed progressively increasing proteinuria after 4 wk and group 3 animals developed proteinuria by 24 wk. Allografts in groups 2 and 4 were morphologically unremarkable at 24 wk. Kidneys of group 1 animals rapidly developed changes of acute rejection, and those that survived long-term showed extensive glomerulosclerosis and interstitial fibrosis. Changes of early chronic rejection were noted in group 3 grafts. By reverse transcriptase–PCR, expression of representative inflammatory factors interferon-γ and interleukin-10 were significantly elevated at 24 wk only in the surviving group 1 animals. A single dose of a signaling anti-CD28 mAb administered at transplantation or in combination with a short course of CsA significantly prolonged recipient survival, normalized function, and preserved the morphology of renal allografts in an established model of chronic rejection. These data support an important role for T cell costimulation in the evolution of the chronic process.


2007 ◽  
Vol 14 (10) ◽  
pp. 1334-1341 ◽  
Author(s):  
Yeddula Narayana ◽  
Beenu Joshi ◽  
V. M. Katoch ◽  
Kanhu Charan Mishra ◽  
Kithiganahalli N. Balaji

ABSTRACT The multigene PE and PPE family represents about 10% of the genome of Mycobacterium tuberculosis. Here, we report that three members of the PE family, namely, Rv1169c, Rv0978c, and Rv1818c, elicit a strong, but differential, B-cell humoral response among different clinical categories of tuberculosis patients. The study population (n = 211) was comprised of different clinical groups of both adult and child patients: group 1 (n = 94) patients with pulmonary infection, group 2 (n = 30) patients with relapsed infection, group 3 (n = 31) patients with extrapulmonary infections, and clinically healthy donors (n = 56). Among the PE proteins studied, group 1 adult patient sera reacted to Rv1818c and Rv0978c, while Rv1169c elicited immunoreactivity in group 3 children. However, all three PE antigens studied as well as the 19-kDa antigen did not demonstrate humoral reactivity with sera from group 2 patients with relapsed infection. The current study shows that while responsiveness to all three PE antigens is a good marker for M. tuberculosis infection, a strong response to Rv0978c or to Rv1818c by group 1 adult patients with pulmonary infection or largely restricted reactivity to Rv1169c antigen in child patients with extrapulmonary infections offers the possibility of differential utility in the serodiagnosis of tuberculosis.


Author(s):  
А.Р. Мавзютов ◽  
Р.Р. Гарафутдинов ◽  
А.Р. Габдрахманова ◽  
И.М. Салахов ◽  
И.Д. Тупиев

Липолисахариды (ЛПС, эндотоксины) грамотрицательных бактерий обладают выраженной биологической активностью, в том числе терапевтической, однако для S. meliloti таких данных нет. Цель работы - экспериментальное изучение гемопоэтической активности 4 фракций липополисахаридов, выделенных из S. meliloti, при индуцированном иммунодефиците у мышей. Методика. Сформировано 7 групп лабораторных мышей (по 10 особей в каждой): 1-я группа - интактные (контроль 1), 2-я - 7-я группа - мыши с иммунодефицитным состоянием, индуцированным однократным внутрибрюшинным введением циклофосфамида. Через 1 сут после моделирования иммунодефицита в течение 21 сут ежедневно мышам 3-й группы вводили препарат сравнения Ликопид® (химическое название: [4-O-(2-ацетиламино-2-дезокси-β-D-глюкопиранозил)-N-ацетилмурамил]-L-аланил-D-α-глутамиламид - синтетический аналог бактериальных гликопептидов из группы иммуностимулирующих средств). Мышам 4-7-й групп - вводили исследуемые фракции липолисахаридов - ЛПС-1, ЛПС-2, ЛПС-3 и ЛПС-4 соответственно. Для ликопида разовая доза составляла 0,1 мл (0,05 мг/мл), для исследуемых фракций ЛПС S. meliloti - 0,2 мл (10 пг/мл). Иммунодефицитным мышам 2-й группы фракции липополисахаридов и препарат сравнения Ликопид® не вводили Через 21 сут мышей выводили из эксперимента. Изучали весовые характеристики органов подопытных животных и лейкоцитарную формулу. Результаты. Введение мышам на фоне вторичного экспериментального иммунодефицита ликопида сопровождалось снижением количества палочкоядерных нейтрофилов и моноцитопенией; при введении фракции ЛПС-1 возрастало количество сегментоядерных нейтрофилов; ЛПС-2 - имели место снижение содержания палочкоядерных нейтрофилов и лимфоцитоз; ЛПС-3 - наблюдали снижение содержания палочкоядерных нейтрофилов и лимфоцитоз на фоне значимого увеличения количества сегментоядерных нейтрофилов; ЛПС-4 - констатировалось увеличение числа базофилов, снижение содержания палочкоядерных нейтрофилов и лимфоцитоз на фоне значимого увеличения количества сегментоядерных нейтрофилов. Заключение. Фракции ЛПС Sinorhizobium meliloti проявляют модулирующие эффекты, схожие с механизмами «экстренного миелопоэза» при физиологичном варианте течения бактериальных инфекций. Lipolysaccharides (LPS, endotoxins) of gram-negative bacteria have a pronounced biological activity, including therapeutic activity; however, there is no such data for S. meliloti. Aim. To conduct an experimental study of hematopoietic activity of four lipopolysaccharide fractions isolated from S. meliloti under induced immunodeficiency in mice. Methods. 7 groups of 10 laboratory mice each were formed: group 1, intact mice (control 1); groups 2-7, mice with immunodeficiency induced by a single intraperitoneal injection of cyclophosphamide. Mice of group 3 were daily injected with a comparison agent, Licopid® (Chemical name: [4-O- (2-acetylamino-2-deoxy-β-D-glucopyranosyl) -N-acetylmuramyl] -L-alanyl-D-α-glutamyl amide; single dose, 0.1 ml (0.05 mg/ml)) for 21 days starting one day after the induction of immunodeficiency. Mice of groups 3-7 were injected with the studied S. meliloti LPS fractions, LPS-1, LPS-2, LPS-3, and LPS-4, respectively (single dose, 0.2 ml (10 pg/ml)). Immunodeficient mice of group 2 received neither the comparison agent, Licopid® nor LPS fractions. The mice were euthanized at 21 days. Weight characteristics of animal organs and white blood count were studied. Results. Administration of Licopid® to mice with secondary experimental immunodeficiency was associated with decreased count of stab neutrophils and monocytopenia; LPS-1 fraction increased the count of segmented neutrophils; LPS-2 decreased the count of stab neutrophils and induced lymphocytosis; LPS-3 decreased the count of stab neutrophils and induced lymphocytosis associated with a significant increase in the count of segmented neutrophils; LPS-4 induced basophilia, decreased count of stab neutrophils, and lymphocytosis associated with a significant increase in the count of segmented neutrophils. Conclusion. Sinorhizobium meliloti LPS fractions exerted modulating effects similar to the mechanisms of “emergency myelopoiesis” in the physiological course of bacterial infections.


2020 ◽  
pp. 021849232096643
Author(s):  
Serdar Gunaydin ◽  
Orhan Eren Gunertem ◽  
Seyhan Babaroglu ◽  
Atike Tekeli Kunt ◽  
Kevin McCusker ◽  
...  

Background Despite the increasing popularity of single-dose cardioplegia techniques in coronary artery bypass grafting, the time window for successful reperfusion remains unclear. This study aimed to compare different cardioplegic techniques based on early and 30-day clinical outcomes via thorough monitoring. Methods This prospective cohort study included high-risk patients undergoing coronary artery bypass grafting and receiving 3 different types of cardioplegia between January 2017 and June 2019. Group 1 ( n = 101) had a single dose of del Nido cardioplegia, group 2 ( n = 92) had a single dose of histidine-tryptophane-ketoglutarate, and group 3 ( n = 119) had cold blood cardioplegia. Patients were examined perioperatively by memory loop recording and auto-triggered memory loop recording for 30 days, with documentation of predefined events. Results Interleukin-6 and cardiac troponin levels in group 1 were significantly higher than those in groups 2 and 3. The incidence of predefined events as markers of inadequate myocardial protection was significantly higher group 1, with more frequent atrial fibrillation attacks and more hospital readmissions. The readmission rate was 17.6% in group 1, 9% in group 2, and 8% in group 3. Conclusions Our data demonstrate the long-term efficacy of cardioplegic techniques, which may become more crucial in high-risk patients who genuinely have a chance to benefit from adjunct myocardial protection. Patients given del Nido cardioplegia had a significantly more prominent inflammatory response and higher troponin levels after cardiopulmonary bypass. This group had issues in the longer term with significantly more cardiac events and a higher rehospitalization rate.


Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1403
Author(s):  
Yang Ho ◽  
Tzen-Wen Chen ◽  
Tung-Po Huang ◽  
Ying-Hwa Chen ◽  
Der-Cherng Tarng

Serum bilirubin levels, which are determined by a complex interplay of various enzymes, including heme oxygenase-1 (HO-1) and uridine diphosphate–glucuronosyl transferase (UGT1A1), may be protective against progression of cardiovascular disease (CVD) in hemodialysis patients. However, the combined effect of HO-1 and UGT1A1*28 gene polymorphisms on CVD outcomes among hemodialysis patients is still unknown. This retrospective study enrolled 1080 prevalent hemodialysis patients and the combined genetic polymorphisms of HO-1 and UGT1A1 on serum bilirubin were analyzed. Endpoints were CVD events and all-cause mortality. Mean serum bilirubin was highest in patients with S/S + S/L of the HO-1 promoter and UGT1A1 7/7 genotypes (Group 1), intermediate in those with S/S + S/L of the HO-1 promoter and UGT1A1 7/6 + 6/6 genotypes (Group 2), and lowest in the carriers with the L/L HO-1 promoter and UGT1A1 7/6 + 6/6 genotypes (Group 3) (p < 0.001). During a median follow-up of 50 months, 433 patients developed CVD. Compared with patients in Group 3, individuals among Groups 1 and 2 had significantly lower risks for CVD events (adjusted hazard ratios (aHRs) of 0.35 for Group 1 and 0.63 for Group 2), respectively. Compared with the lower bilirubin tertile, the aHRs were 0.72 for the middle tertile and 0.40 for the upper tertile for CVD events. We summarized that serum bilirubin as well as HO-1 and UGT1A1 gene polymorphisms were associated with CVD among patients receiving chronic hemodialysis.


2019 ◽  
Vol 44 (2) ◽  
pp. 141
Author(s):  
Abdul Malik

The objective of this study was to evaluate of Effect of injection Prostaglandin F2α on the time required for onset of estrus and estrus durations in Bali cattle with differences of Paritas. A total of 24 Bali cows were divided into four groups, each group was consisting of 6 cows.  Group 1 samples is heifer’s, group 2, samples was paritas1, group 3, samples was paritas 2 and group 4, samples was paritas 3.  All  cows were normal  tract of reproduction  with showing regular cyclic activities and having active of corpus luteum. The parameters in this study were determined including the time required for onset of estrus and duration of estrus. The result showed that percentage estrus response and duration of estrus were non-significant difference (P>0.05) between heifers and paritas 1, 2, and 3 after estrus synchronization with single dose of prostaglandin F2α. It was concluded that injection of PGF2α on heifers and Paritas 1,2 and 3 were  similar result on the time required for onset of estrus and duration of estrus.


Author(s):  
Özden Kutlay ◽  
Arzu Keskin-Aktan ◽  
Esra Aslan

Cyclophosphamide is a chemotherapeutic drug that is widely used in the clinic and can cause multi-organ toxicity. Apelin-13 is an endogenous adipocytokine with antioxidant properties. Therefore, this study aimed to investigate the possibility of apelin-13 being a potential therapeutic agent on cardiac toxicity and nephrotoxicity caused by cyclophosphamide. In this study, a total of 4 groups were formed, including 8 rats in each group. Group 1: The control group was administered only saline (ip). Group 2: Cyclophosphamide, a single dose of 200 mg/kg (ip) on day 7. Group 3: Apelin-13 (15 μg/kg), for 7 days (ip). Group 4: Administering apelin-13 (15 μg/kg) (ip) for 7 days and a single dose of cyclophosphamide (200 mg/kg) (ip) on day 7, the rats were sacrificed on day 8. LDH, cTn1, cK-Mb, AST, ALT, ALP, MDA, creatinine, and BUN were found to be high in the cyclophosphamide group, however, these values were reduced with apelin-13 administration. Antioxidant enzymes such as SOD, GPx, CAT, and GSH decreased in the cyclophosphamide group, apelin-13 increased these enzyme activities. In addition, histopathological examinations also supported the results obtained. The findings of this study showed that apelin-13 has a protective effect against cardiorenal toxicity caused by cyclophosphamide.


Author(s):  
Mayoukh Kumar Chakraborty ◽  
Shalini Gainder ◽  
Subhas Chandra Saha ◽  
Rashmi Bagga

Background: Single dose methotrexate is the most preferred method of non-surgical management of unruptured tubal ectopic. A 2-dose regimen is suggested to treat tubal ectopic with higher trophoblastic cell load. Minimally invasive technique of ultrasound guided intracardiac KCL instillation along with systemic methotrexate has been in use even for live ectopic pregnancy. Objective of the study was to evaluate the success rate of single dose regimen of MTX (Methotrexate), 2-dose regimen of MTX and ultrasound guided instillation of intracardiac KCl in three different cohort of unruptured tubal ectopic pregnancy with an attempt to increase success of non-surgical management.Methods: Fifty-eight women with unruptured tubal ectopic pregnancy were assigned to treatment protocols according to the initial β-HCG levels and presence/absence of FCA (fetal cardiac activity). Group 1: presence of FCA in the tubal ectopic; Group 2: initial β-HCG ≤5000 IU/ml; Group 3:  initial β-HCG ≥5000 IU/ml without FCA. Women in group 1 were treated with ultrasound guided instillation of intracardiac KCl combined with systemic MTX. While women in group 2 were administered single dose regimen of MTX and group 3 received 2-dose regimen of MTX.Results: Overall success rate of non-surgical management was 89.3% across all groups. Success rate in Group 1 was 78.6%. Success rate was 93.1% in group 2 while 92.3% in group 3. Rupture rate was 1.7% in the present study.Conclusions: For non-surgical management categorizing and treating is an option with good result. Women with presence of cardiac activity can opt for non-surgical option with likely resolution in 78% cases.


Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1130
Author(s):  
Claudius Speer ◽  
Matthias Schaier ◽  
Christian Nusshag ◽  
Maximilian Töllner ◽  
Mirabel Buylaert ◽  
...  

It has been demonstrated that patients on hemo- or peritoneal dialysis are particularly susceptible to SARS-CoV-2 infection and impaired seroconversion compared to healthy controls. Follow-up data on vaccination response in dialysis patients is limited but is greatly needed to individualize and guide (booster) vaccination strategies. In this prospective, multicenter study we measured anti-spike S1 and neutralizing antibodies in 124 hemodialysis patients, 41 peritoneal dialysis patients, and 20 age- and sex-matched healthy controls over 12 weeks after homologous BNT162b2 vaccination. Compared to healthy controls, both hemodialysis and peritoneal dialysis patients had lower anti-S1 IgG antibodies (median (IQR) 7.0 (2.8–24.3) and 21.8 (5.8–103.9) versus 134.9 (23.8–283.6), respectively; p < 0.001 and p < 0.05) and a reduced SARS-CoV-2 spike protein–ACE2 binding inhibition caused by vaccine-induced antibodies (median (IQR) 56% (40–81) and 77% (52–89) versus 96% (90–98), respectively; p < 0.001 and p < 0.01) three weeks after the second vaccination. Twelve weeks after the second vaccination, the spike protein–ACE2 binding inhibition significantly decreased to a median (IQR) of 45% (31–60) in hemodialysis patients and 55% (36–78) in peritoneal dialysis patients, respectively (p < 0.001 and p < 0.05). Peritoneal dialysis patients mounted higher antibody levels compared with hemodialysis patients at all time points during the 12-week follow-up. Individual booster vaccinations in high-risk individuals without seroconversion or rapidly waning neutralizing antibody levels are required and further data on the neutralization of emerging variants of concern in these patients are urgently needed.


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