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1.
Indian Journal of Transplantation ; 16(4):458-460, 2022.
Article in English | EMBASE | ID: covidwho-2217248

ABSTRACT

The novel coronavirus (severe acute respiratory syndrome coronavirus [SARS-CoV-2]) has spread out to most of the world with the World Health Organization (WHO) classifying it as a global pandemic. There exists very little information on the infectious course of COVID-19 in immunocompromised individuals, including transplant recipients. We report a case of a young adult who tested positive for SARS-CoV-2 in the immediate postoperative period following renal transplantation. Copyright © 2022 Indian Journal of Transplantation.

2.
Swiss Medical Weekly ; 152(Supplement 266):34S, 2022.
Article in English | EMBASE | ID: covidwho-2207661

ABSTRACT

Background: Long-term survival of kidney allografts is limited by either inadequately controlled rejection and/or by side effects of long-term immunosuppression (drug toxicity, infections and neoplasia). Induction of donor-specific tolerance would resolve most, if not all of these limitations. Here, we report on 6 patients included in the first European trial of combined kidney and hematopoietic stem cell transplantation (HSCT;swisstolerance. CH). Methods or Case description: Six patients (3 female / 3 male) underwent combined kidney and hematopoietic stem cell transplantation from their HLA-identical living siblings between 2016 and 2022. Conditioning therapy for HSCT and immunosuppression was performed according to the Stanford protocol including total lymphoid irradiation, anti-thymocyte globulin followed by corticosteroids (3 days), mycophenolate (1 months) and cyclosporine for 6-15 months. After 9-15 months all immunosuppression was withdrawn. Results or Learning points: Five out of six patients were completely withdrawn from all immunosuppression (follow-up between 6 years and 4 months). No rejection or graft-versus-host disease episodes and no relevant infections occurred. Initial donor chimerism was seen in all patients. However, in 5/6 patients the chimerism level was declining, whereas one patient remained a stable mixed chimera. Specificity of tolerance was tested by molecular microscope analysis (absence of rejection signature) and by successful SARS CoV2 vaccination in some of the patients. One patient experienced a relapse of her primary glomerulonephritis in the allograft. She developed proteinuria, but renal function remained normal so far. Conclusion(s): Combined HSCT and kidney transplantation from the same living donor provides tolerance to a kidney allograft. This tolerance is donor-specific, as shown by protective immune responses against a SARS-CoV2-specific vaccine and absence of "molecular rejection".

3.
European Geriatric Medicine ; 13(Supplement 1):S405-S406, 2022.
Article in English | EMBASE | ID: covidwho-2175456

ABSTRACT

Background: Biologic and immunosuppressive therapies play important roles in the management of a wide variety of dermatologic diseases. However, immunotherapies can negatively affect normal immune functioning, placing these patients at risk of infection [1]. The strength of the immune system also declines with increasing age. Vaccinations reduce the risk of susceptibility to infections. Thus, it is recommended that vaccinations against influenza, pneumococcal and COVID-19 infections are given to boost patient's defence while on immunosuppressant medications [2]. In addition, people over 65 years are at the highest risk of serious illness from COVID-19 if they have not been vaccinated [3]. Therefore, in accordance with the British Association of Dermatology guidelines (August 2021), patients on biologic therapies can and should have their COVID-19, influenza and pneumococcal vaccinations [2, 4]. MethodologyWe conducted a retrospective audit of all patients over the age of 65 years on biological therapies in the dermatology clinic between March 2021 and March 2022. Data on patients COVID-19, influenza and pneumococcal vaccination status were obtained from the departmental dermatology database (Filemaker Pro) and patients' medical records. In patients where the vaccine status wasn't documented in their medical records these patients were telephoned about their vaccine status. Findings were compared with the British association guidelines [2, 4], which were our audit standard. The data was subsequently analysed using Microsoft Excel. ResultsEighteen patients over the age of 65 years, were on biological therapies in the Dermatology Department, between March 2021 and March 2022. 44% (n = 8) of patients were between 65 and 70 years old, 28% (n = 5) were between 70 to 75 years old and 28% (n = 5) were above 75 years. The mean age was 71 years (+/- sd 5.2). The gender distribution was equal: 50% (n = 9) male, 50% (n = 9) female. Biologic therapies were indicated for treatment of psoriasis in 94% (n = 17) of patients and for treatment of eczema in one patient (6%). With regard to biological therapies, 17% (n = 3) of patients were treated with adalimumab, 16% (n = 3) were receiving Etanercept, 28% (n = 5) were receiving secukinumab, 11% (n = 2) were receiving ixekizumab, 11% (n = 2) were receiving guselkumab, 5% (n = 1) were receiving ustekinumab, 5% (n = 1) were receiving dupilumab and 5% (n = 1) were receiving risankizumab. All patients (100%, n = 18) had received all three of their COVID-19 vaccines. 50% (n = 8) were awaiting their 4th covid vaccination. 94% (n = 17) of patients had received their influenza vaccine in 2021. 66% (n = 12) of patients had received their pneumococcal vaccination in the last 5 years. We advised the patients who had not received their recommended vaccinations to receive it. Conclusion(s): This audit confirms dermatology patients over the age of sixty-five years, demonstrate excellent compliance receiving their covid-19 vaccinations, as recommended by the BAD2,4. This is important as patients over 65 years who are unvaccinated are recognised as being at the highest risk of serious infection from COVID-19. However, only 66% of patients had received their pneumococcal vaccination in the previous 5 years in contrast with 94% who had received their influenza vaccine in 2021, illustrating the need for educational intervention on the importance of all three vaccinations in this high risk patient group. We plan to perform a reaudit next year to assess compliance with vaccinations following patient education in order to complete the audit cycle.

4.
European Geriatric Medicine ; 13(Supplement 1):S179-S180, 2022.
Article in English | EMBASE | ID: covidwho-2175449

ABSTRACT

Introduction: The metabolic syndrome and its associated comorbidities, such as diabetes, have rapidly emerged as predictive factors of severe disease and even mortality in patients with Covid.19 In the recent literature, metformin has been suggested as a protective factor against mortality. Material(s) and Method(s): This is a retrospective study of patients hospitalised between March 2020 and September 2021, aged 75 years and older, in the Jolimont network for Sars-cov 2 infection and with a history of diabetes. We examined clinical, biological and radiological data. Histories such as hypertension, obesity, renal failure, COPD, immunosuppression and its treatment as well as glycosylated haemoglobin and BMI were analysed. We also indicated the degree of percentage of parenchyma affected on the lung scan and if there was an admission to intensive care. Result(s): The study included 84 patients on chronic metformin and 102 patients on antidiabetic therapy without metformin. There was no significant difference between the two groups in terms of BMI, comorbidities, presence or absence of pulmonary embolism, there was no difference in the severity of chest CT in our two groups (on or off metformin, despite the fact that the second group had a higher mortality rate). Of note, the study group had a low rate of ICU admission (3.6%). Conclusion(s): We did not observe a more severe radiological impairment in both groups nor a difference in ICU admission despite a higher mortality in diabetics without metformin.

5.
Indian Journal of Hematology and Blood Transfusion ; 38(Supplement 1):S74-S75, 2022.
Article in English | EMBASE | ID: covidwho-2175107

ABSTRACT

Introduction: Untreated/refractory severe aplastic anemia (SAA) is associated with very high mortality. Allogenic bone marrow transplantation or immunosuppressive therapy remains mainstay of treatment but these treatments are timely available to only a select subset of patients. Recently eltrombopag has been approved for treatment of SAA. Aims & Objectives: We aimed to describe clinical profile and treatment response in patients with SAA from a tertiary care centre. Material(s) and Method(s): A retrospective analysis of patients diagnosed with SAA over a period of 7 years from January 2015-December 2021 was performed. The details of demographic profile, laboratory features, treatment given and response were analyzed. Result(s): Ninety patients were diagnosed with SAA during this period out of which 18 patients went elsewhere for treatment. Seventy-two patients who received treatment in our hospital were included in the analysis. Sixty-two patients were SAA while 10 VSAA. PNH screening was done in 24 patients, out of which 17 (70%) had small clone. The details of treatment and response achieved is shown in Table 1. Eight patients (11.1%) received matched related donor allogenic hemopoietic cell transplant, out of which one had rejection followed by auto recovery while one died 6 months later due to covid 19 disease. Sixty-four patients received immunosuppressive therapy, forty-nine (76%) responded. Recurrence of SAA occurred in two patients who has achieved complete response to ATG therapy;one received second course of horse ATG + CSA + ETP and responded again. Conclusion(s): Timely diagnosis and appropriate treatment selection is of utmost importance to achieve optimal outcome in severe aplastic anemia. Eltrombopag has become an important addition not only in front line but also in relapsed refractory aplastic anemia. Patients lacking donor, or resources for ATG should be treated with cyclosporine and eltrombopag as early as possible. (Table Presented).

6.
Neurological Sciences ; 43(Supplement 1):S462-S463, 2022.
Article in English | EMBASE | ID: covidwho-2174295

ABSTRACT

Background: Vaccination campaign to contrast the spread of SARSCoV- 2 has raised the issue of vaccine immunogenicity in frail populations, especially multiple sclerosis (MS) patients on disease modifying therapies (DMTs). Material(s) and Method(s): Before (T0) and after 2 months from booster dose of mRNABNT162b2 vaccine (T1), MS patients under DMTs and healthy donors (HDs) were enrolled. For both T0 and T1, anti-Spike (S) antibody titer as well as IFNg, IL2 and TNFa T cells production upon S peptide libraries stimulation were assessed. According to DMTs mechanism of action, MS patients were stratified into immunosuppressive (such as fingolimod, cladribine, ocrelizumab, and alemtuzumab) and immunomodulating (natalizumab) groups [1]. "Activated" cells were defined as T cells producing any of IFNg or IL2 or TNFa while polyfunctional T cells were defined as those simultaneously producing all 3 cytokines. All possible combinations of intracellular expression of IFNg, IL2, and TNFa in cytokine-producing T cells were evaluated. Result(s): Sixteen MS patients (11 females/5 males, median age [IQR] 41.5 [34.3-48.8] years) and nine HDs (7 females/2 males) were enrolled. An increase of anti-S antibody titers at T1 compared to T0 in bothMSand HDs was seen (1930 [85.75-5895] and 198.5 [80.73-1140] BAU/ml, respectively, p=0.0017;3590 [1575-10850] and 320 [124.1- 662.0], respectively, p=0.0039). Reduced percentage of CD4 and CD8 "activated" and CD4 polyfunctional T cells were observed inMS compared toHDs at T0 (CD4: 1.025 [0.795-1.275] and 1.640 [1.325-2.245], respectively, p=0.0111;CD8 1.0 [0.603-1.328] and 1.65 [1.315-2.360], respectively, p=0.0135;CD4: 0.045 [0.029-0.089] and 0.10 [0.10-0.125], respectively, p=0.0211). Stratifying MS population, only immunomodulating showed an increase in anti-S antibody titers production at T1 (5410 [2655-9893] and 871 [175.3-1360], respectively, p=0.0313), while a reduced production was seen in immunosuppressive compared to immunomodulating and HDs (369.5 [49.8-1975] and 5410 [2655-9893], respectively, p=0.0172;369.5 [49.8-1975] and 3590 [1575-10850], respectively, p=0.0431]. At T0 in immunosuppressive patients a reduced percentage of "activated" CD4 and CD8 T cells was observed when compared to HDs (0.875 [0.658-1.025] and 1.64[1.325-2.245], respectively, p=0.0020;0.91[0.53-1,293] and 1.65[1.315-2.36], respectively, p=0.019). While, at T1 a reduced percentage of CD8 polyfunctional T cells was seen in immunosuppressive patients when compared to HDs (0.036[0.019-0.065] and 0.1[0.048- 0.1291], respectively, p=0.0232). Conclusion(s): Both humoral and T cell specific response to vaccination in MS patients seems to be significantly influenced by different DMTs mechanism. Moreover, a higher percentage of TNFa and a reduced IFNg production was observed, mainly in immunosoppressive group.

7.
Minerva Respiratory Medicine ; 61(4):215-216, 2022.
Article in English | EMBASE | ID: covidwho-2205205
8.
Indian Journal of Nephrology ; 32(7 Supplement 1):S129, 2022.
Article in English | EMBASE | ID: covidwho-2201599

ABSTRACT

BACKGROUND: In the presence of COVID-19 illness immunosuppressed patients such as kidney transplant recipients (KTRs) have a higher mortality risk. ABO incompatible KTRs (ABOi - KTRs) are high-risk transplants and the use of lowdose maintenance immunosuppression during the COVID-19 pandemic is unknown. AIM OF THE STUDY: To study effect of low dose maintenance immunosuppressive therapy on graft function and immunologic events in patients following ABOi-KTRs during COVID-19 pandemic. METHOD(S): We present the results of a follow-up study of eight ABOi-KTRs done in Kidney Transplant Unit at Jaslok Hospital during COVID-19 pandemic. RESULT(S): Seven (87%) of the eight patients were male, while one was female. The median age was 49 years. Prior to transplant, all patients received rituximab (500 mg) and plasmapheresis. Six (75%) patients received antithymocyte globulin (1 mg/kg) induction, while two (25%) received basiliximab. Dose of one immunosuppressive agent tacrolimus was decreased to trough level of 6 to 8 ng/ mL instead of 8 to 12 as compared to our institutional protocol in pre-covid era. Antimetabolites and steroids were used in usual doses. Although immunosuppression was decreased, no rejection episodes or infection observed up at 10 days, 1 and 3 month after discharge, and no significant changes occurred in creatinine level during same period. Acute graft dysfunction was seen in 1 patient and the severity was related to tacrolimus trough levels, which were higher. All patients recovered baseline kidney function with no mortality during follow-up. CONCLUSION(S): Our observational study suggests that the reduction of tacrolimus dose in ABOi KTRs performed during COVID-19 appears to be safe, since no patient experienced rejection episodes.

9.
Indian Journal of Nephrology ; 32(7 Supplement 1):S29, 2022.
Article in English | EMBASE | ID: covidwho-2201593

ABSTRACT

BACKGROUND: A significant reduction of acute rejection rates was observed after using Mycophenolate mofetil (MMF) in renal transplant recipients (RTR). However side-effects like hematological and gastrointestinal intolerance often occur when MMF is used in routine doses. MMF dose reduction is required during its side-effects or coexisting infection in RTR. The outcome of MMF dose modulation in RTR is not well established AIM OF THE STUDY: COVID-19 pandemic has given an opportunity to study the effect of MMF dose modulation on graft function as large number of RTR who had COVID-19 received MMF dose reduction or discontinuation. This study's objective was to determine whether MMF dose reduction or discontinuation was associated with the effect on allograft function after renal transplantation. We included all RTR who had an infection with SARS-CoV2 and received MMF dose reduction or discontinuation METHODS: We prospectively collected data of renal transplant recipients developing COVID-19 infection during the first and second covid waves. Management including decision on admission immunosuppression modulation antibiotics were done based on clinician'S discretion subject to logistics and the prevailing guidelines by the ISOT. All patients were followed up for minimum 15 months for graft dysfunction biopsy rate biopsy-proven acute rejection ( BPAR). The effect of immunosuppression modulation - MMF cessation (Group A) Vs MMF reduction/no manipulation (Group B) and its bearing on the incidence of rejection and was compared. Additional factors such as follow - up sub therapeutic CNI levels development of DSA ( when done ) steroid increment were studied regression model. Kaplan - Meier survival curves for 24 months drawn. RESULT(S): Among 251 renal transplant patients with SARSCoV2 infection, 38 patients died during Index admission. 45 patients have not completed for 15 months. 168 patients completed 15 month follow - up. Among them, antimetabolite were reduced in 115 (68.5%), stopped in 42 (25%), not manipulated in 5 ( 3%) and 6 patients were not on anti-metabolites and hence excluded from present analysis. Of the 162 patients, MMF had been stopped for 2 weeks or until presumed clinical recovery in 42 patients ( Group A) and the rest in 120 patients ( Group B). Mean age was 41.18 ( i' +/- 12.8), and 75.6% had mild COVID. Median duration of followup was 18 months ( 14q1-22q3 months). Total readmission rate was 66 (40.7%) (Group A 21 (50%) Vs Group B 45 (37.5%). Graft biopsy was done in 16% of patients. 9.3% patients had acute rejection (11.9% Vs 8.3%, p 0.05). Among those who had rejection, ABMR was seen in 2, ACR in 3, CABMR in 5 and combined rejection in 1 CONCLUSION(S): MMF dose modulation to tackle an infectious episode may be associated with graft dysfunction and rejection on follow-up and close follow-up is needed in any patient in whom MMF dose in manipulated.

10.
Indian Journal of Nephrology ; 32(7 Supplement 1):S67, 2022.
Article in English | EMBASE | ID: covidwho-2201587

ABSTRACT

BACKGROUND: COVID-19 has been associated with high morbidity and mortality in renal transplant recipients. However, risk factors for COVID-19 disease in patients with kidney transplants remain poorly defined. The outcome following vaccination in renal transplant recipients is less reported. AIM OF THE STUDY: To assess effect of vaccination in renal transplant recipients with COVID-19 METHODS: We enrolled patients who underwent kidney transplantation at our center who tested positive for COVID-19 from the beginning of the pandemic till June 2022. Patients were screened for baseline and transplant characteristics functional parameters comorbidities immunosuppressive therapies vaccination status and treatment received. COVID-19 disease severity was assessed. Patients were followed up during the pandemic until June 2022 of those admitted or home quarantined via teleconsultation. Data was collected compiled and analyzed. RESULT(S): A total of 85 renal transplant recipients with COVID-19 infection were studied. The mean age was 42.5 years. Nine were not vaccinated, 11 had taken 1 dose of vaccination, and rest completed 2 doses of vaccination. 23 had received antibody cocktail, 65 survived, and 20 succumbed to COVID-19. A total of 48 of them had graft dysfunction, 22 had severe graft dysfunction requiring hemodialysis. Among those who expired only had received antibody cocktail, all of them had severe graft dysfunction and only 2 were not vaccinated. Among those who expired most expired in the second wave of the pandemic. CONCLUSION(S): Renal transplant recipients with COVID-19 have a high risk of mortality. Comorbidities like obesity, diabetes mellitus, asthma, and chronic pulmonary disease were associated with higher risk of developing COVID-19 disease. Effect of vaccination and outcome of COVID-19 infection in renal transplant recipients is under reported. There is risk of severe COVID-19 infection despite vaccination. Therefore, safety preventive measures to be continued. More work needed to find a definitive treatment for COVID-19 infection and much more efficacious vaccines and vaccination strategies to be designed.

11.
Open Forum Infectious Diseases ; 9(Supplement 2):S463, 2022.
Article in English | EMBASE | ID: covidwho-2189744

ABSTRACT

Background. Corona virus disease-19 (Covid-19) has significantly affected organ transplantation with concerns regarding severe infection and mortality. Data on Covid-19 in renal transplant recipients (RTRs) is scarce from Pakistan. The aim of this study is find out the factors effecting mortality among Covid-19 patients in renal transplant recipients from the largest transplant center of Pakistan. Methods. All RTRs >18 years, with positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) and diagnosed as severe disease, between April to December 2020 were retrospectively reviewed. The severe disease was defined as O2 saturation < 94% at room air on admission. Survivors and non- survivors were compared. Demographics, immunosuppression, comorbid conditions, clinical features, laboratory investigations and graft function were noted. Results. A total of 95 RTRs had severe disease. There was no difference in mortality between age, gender and co-morbid conditions among survivors and nonsurvivors. Both groups received similar immunosuppressive regimen. Intensive care unit (ICU) admission [16.5% vs 68.8% p< 0.001 OR 11.17 95% CI (3.3-37.6)] and high D-dimers >1.5mug/ml (p=0.052) at the time of admission were significantly associated with mortality. There was no association of graft function with mortality. Treatment with methyl-prednisolone was found to be significantly associated with survival [83% vs 43% P=0.02 OR 0.15 95% CI (0.05-0.49)]. (Table 1) WHO grading of the disease is shown in figure 1, there was a 100% mortality among patients on mechanical ventilator. Conclusion. ICU admission and high D-dimers at the time of admission are the significant risk factors for mortality in patients with Covid-19 infection. There was no association of graft dysfunction with mortality. Steroids use has significantly improved survival in renal transplant recipients with severe Covid-19 infection.

12.
The Lancet Infectious Diseases ; 22(12):1676, 2022.
Article in English | EMBASE | ID: covidwho-2150865
13.
Multiple Sclerosis Journal ; 28(3 Supplement):133-134, 2022.
Article in English | EMBASE | ID: covidwho-2138894

ABSTRACT

Neuromyelitis optica spectrum disorders (NMOSD) is an immunemediated inflammatory disorder of the central nervous system. SARS-CoV-2 infections not only affect the lungs but generally all organs including the central nervous system. The underlying pathophysiology for SARS-CoV-2 associated CNS disease is suspected to be immunogenic. Therefore, the question is whether COVID-19 can trigger relapses in NMOSD patients. On the other hand, there have been reports that COVID-19 vaccination may trigger a relapse. The aim of our study was to assess the risk of NMOSD relpase after SARS-CoV-2 infection or after vaccination. Department of Neurology Medical University of Warsaw is a reference center for treatment of NMOSD patients in Poland. Nowadays we are taking care on seventy-five patients meeting NMOSD diagnostic criteria. As of March 31, 2022, we registered 47 SARS-CoV-2 infections. Twenty-two SARS-CoV-2 infections were reported in patients prior to COVID-19 vaccination (19 females, 3 males). Mean age of patients was 49+/-10 years, mean EDSS 4.5+/-1.5. Twenty (90.9%) patients were on immunosuppressive therapy (rituximab -11, steroids-4, inebilizumab -2, azathioprine -1, satralizumab -1, mycophenolate mofetil -1). Twenty-five SARS-CoV-2 infections occurred after the full course of vaccination (23 females, 2 males). Mean age of patients was 50+/-12 years, mean EDSS 3.6+/-1.7. Twenty-three (92%) patients were on immunosuppressive therapy (rituximab - 12, inebilizumab - 1, azathioprine - 3, satralizumab - 3, mycophenolate mofetil - 4). Three patients had a relapse after COVID-19 (within three months). Two of these people were still unvaccinated at the time. These patients were not receiving full immunosuppressive treatment at the time (one patient developed COVID-19 right after the first dose of rituximab, the other patient received the last dose of rituximab 18 months earlier). The third patient was treated with rituximab and was fully vaccinated. NMOSD relapse occurred in 6% of patients confirmed with COVID-19. Thee risk of relapse was even lower (2%) among patients properly treated with immunosuppressants. Of our seventy-five patients, only two were not vaccinated against SARS-CoV-2. All patients receivedmRNA SARS-CoV-2 vaccines. No vaccine-related NMOSD attack has been reported. Conclusion(s): Patients with NMOSD treated with immunosuppressants have a low risk of a relapse due to COVID-19 infection. In our study mRNA COVID-19 vaccines do not increase the risk of a relapse.

14.
British Journal of Surgery ; 109(Supplement 4):iv2-iv3, 2022.
Article in English | EMBASE | ID: covidwho-2134867

ABSTRACT

Introduction: WHO declared a pandemic of COVID-19 in March 2020. This study analyses the impact of COVID-19 on beta-cell replacement therapy in the UK. Method(s): Pancreas and islet donation and transplant activity in the period March 2020/2021 was compared with the same period the previous year. Result(s): 2,180 patients had a functioning graft during March 2020/2021. 5.8%(n=126) tested positive for COVID-19 and two died (1%). In this period there was a 43% reduction in solid organ donors n=1,615, compared with the previous year, n=2,840. Of the 625 solid organ donors with a pancreas offered, 32% had the pancreas retrieved compared with 51% the previous period. 97 whole pancreas and islet transplants were performed in the UK down 54% from the prior period. Of the 84 pancreas transplant recipients;four tested positive for COVID-19 but none died, and two grafts failed within the first week from vascular thrombosis (neither were COVID-19 positive). Of the 13 SIK and islet alone transplant recipients, two tested positive for COVID-19 but neither died. Of these SIK transplants, one is known to have failed within a month and this is equivalent to that seen in the previous time period. To our knowledge, no patient receiving beta cell replacement therapy died of COVID during the first year of the pandemic despite immunosuppression. Conclusion(s): In the UK, pancreas, and islet transplantation have continued during the pandemic at a lower rate. Outcomes following transplantation within the COVID era are, so far, similar to those in the period prior. Take-home message: Outcomes following transplantation within the COVID era are, so far, similar to those in the period prior.

15.
Research and Practice in Thrombosis and Haemostasis Conference ; 6(Supplement 1), 2022.
Article in English | EMBASE | ID: covidwho-2128211

ABSTRACT

Background: The SARS-CoV- 2 pandemic has led to changes in the way we manage autoimmune disease such as immune thrombocytopenia (ITP). Immunosuppression is a risk factor for severe COVID-19 and also leads to reduced vaccine responses. Medical therapy for ITP is broadly divided into immunosuppressive or that which stimulates megakaryopoeisis. Aim(s): To assess changes in medical therapy for ITP during the SARS-CoV- 2 pandemic using data from the UK adult ITP registry Methods: The UK registry of primary adult ITP (https://www.qmul. ac.uk/itpre gistr y/), one of the largest internationally, produces annual treatment reports on therapy use, trends and to identify cohorts for study. We reviewed data from annual reports to assess treatment changes. Result(s): At the time of analysis, there were 4503 patients in the registry: 224 diagnosed with ITP in 2019, 105 in 2020 and 97 in 2021 (median age 57y, 59y and 55y respectively). Table 1 shows changes in treatment 2019-2021. Most patients still received steroids as part of the treatment for ITP acutely. IVIG use remained static between 2019 and 2021. For diagnoses made between 2019 and 2021 all patients received at least 1 treatment. Immunosuppressive therapy use reduced from pre-2019 levels (data not tabulated) where almost 23% patients received rituximab and 18% MMF to 0% and 3% respectively by 2021. Use of TPO-RA increased, from 33% in 2019 to 43% in 2021. Median time to starting TPO-RA was 3.76 months (IQR 1.317,9.225) in 2019 reducing to 0.985 months (IQR 0.58,1.465) in 2021. Platelet response criteria will undergo analysis once additional data entry has taken place. Conclusion(s): Steroids continue to be used acutely for most ITP patients but TPO-RA are being used ahead of other immunosuppressive therapy in line with interim NHSE pandemic policy. Most patients entered received at least one line of treatment -likely reflecting those frequently attending sites to access healthcare.

16.
Research and Practice in Thrombosis and Haemostasis Conference ; 6(Supplement 1), 2022.
Article in English | EMBASE | ID: covidwho-2128138

ABSTRACT

Background: Both de-novo and relapse of Acquired Haemophilia A (AHA) have been reported following SARS-CoV- 2 infection and vaccination suggesting virus-induced immune dysregulation as a potential mechanism. The current standard of care in the potentially fatal AHA, requires the use of bypassing agents (BPA) or porcine FVIII to achieve haemostasis and immunosuppression to suppress autoantibody production. The bispecific antibody emicizumab now offers the possibility to achieve the former and reduced need for the latter but is only approved solely for use in congenital haemophilia A. Aim(s): We present a cluster of three AHA cases presenting between April to June 2021 at a single tertiary centre. Notably each patient received recent BNT162b2(Pfizer) vaccination. Method(s): Bypassing therapy and steroids were commenced with response in two cases. One case remained refractory to BPA, porcine FVIII, steroids and Azathioprine. Approval was sought for a subcutaneous biweekly injection of Emicizumab in order to avoid rituximab during the pandemic. Result(s): In 10 months since initiation of emicizumab, no further bleeding and no thrombotic events have been reported. Factor VIII (chromogenic) is now detectable in all patients. Conclusion(s): The close interaction between SARS-Cov- 2 and the haemostatic system has been evident in the COVID era. The unusual clustering of cases presented here suggests that antibody responses to SARS-Cov- 2 infection or vaccine may cross-react with coagulation factors resulting in the immunohematological phenomenon of AHA. Furthermore, to our knowledge this is the first use of Emicizumab in acquired haemophilia in the post-partum period. As well as providing excellent haemostatic efficacy and potential cost-effectiveness, emicizumab provides several advantages for a new mother during the COVID-19 pandemic. These include a return to home, contact with family and minimal attendance at hospital as well as avoiding immunosuppression conferring increased risk of infection and loss of protection from vaccinations. We note the recent application for use of emicizumab in AHA.

17.
PM and R ; 14(Supplement 1):S171-S172, 2022.
Article in English | EMBASE | ID: covidwho-2127999

ABSTRACT

Case Diagnosis: Development of Guillain-Barre Syndrome (GBS) or transverse myelitis (TM) shortly following COVID-19 vaccination. Case Description: This case series details three individuals who developed Guillain-Barre Syndrome (GBS) or transverse myelitis (TM) shortly following COVID-19 vaccination. All three of the patients received immunosuppressive therapy as part of their treatment regimen with tailored treatments for their individual deficits. Two of the patients improved with treatment while one patient retained their deficits through their hospitalization course. In this report, we will explore a series of cases in which patients developed autoimmune postvaccination neurological sequelae including TM and GBS. Setting(s): Inpatient and outpatient rehabilitation Assessment/Results: Here, we have presented three cases of post-COVID-19 vaccination neurological sequelae including TM and GBS. The diagnosis was confirmed with MRI and/or lumbar puncture. Treatment regimens had slight variation, but at their cores utilized immunosuppressant therapies. Neurological manifestations improved in two out of the three cases with these forms of treatment. Discussion(s): There have been case studies of TM following MMR and Influenza vaccinations as well. A more common, though still rare, post-vaccine adverse effect is GBS. With the administration of the COVID-19 vaccine, there have been similar reported cases. The frequency of this adverse reaction is not yet determined, and neither are any potential common risk factors. Conclusion(s): Unfortunately, there has not been further support in the determination of risk factors that may make certain patients more prone to these reactions or clarification on the exact pathophysiology underlying these neurological manifestations. Despite these limitations, we can further add to the evidence for TM and GBS as potential adverse effects after COVID-19 vaccination. Additionally, we show that in most cases symptoms improved following immunosuppressive therapies. While further studies will be required to answer some of the above questions, these complications will be an important consideration for future vaccination recipients.

18.
Journal of the American Society of Nephrology ; 33:328, 2022.
Article in English | EMBASE | ID: covidwho-2126105

ABSTRACT

Background: Hemodialysis (HD) patients are vulnerable to COVID-19. Early detection of COVID-19 in dialysis clinics informs isolation and infection control policies. Saliva testing is an alternative to nasopharyngeal swab to detect SARS-CoV-2. The understanding of viral shedding in HD patients is limited. We explore viral shedding duration in HD patients and determine its correlation with immunosuppression. Method(s): Eligible patients diagnosed with COVID-19, confirmed by nasal swab RTPCR within 2 weeks of COVID-19 diagnosis, were recruited. They were given Salivette Saliva Collection kits and instructed to chew a cotton swab for 60 seconds. Result(s): 30 COVID-19 positive patients participated (Table 1). Each patient provided up to 7 saliva samples. 65 samples were collected for an average of 11+/-8 days (range 0-36) after diagnosis. 26 samples showed at least one COVID-19 target gene (N, ORF1ab) with cycle threshold <38 cycles. 12 patients had at least 1 positive sample, and 23 patients had at least 1 negative sample. Of the 23 patients who had at least one negative sample, median days to first negative sample is 9 days (range 0-36). For the 7 patients who only had positive samples, median days to last positive sample is 9 days (range 0-36). There is no observed difference between vaccinated (n=24) and vaccinated patients (n=6). 6 out of 30 patients took immunosuppressants such as Tacrolimus, Hydroxychloroquine, and Mycophenolate sodium. Median days to turn negative (or use last positive date if negative results never achieved) was 15 days for immunocompromised group and 8 days for nonimmunocompromised group (Fig.1) Conclusion(s): Immunocompromised HD patients shed COVID-19 virus for a significantly longer period. While our study did not explore the shedding of viable SARS-CoV-2, a longer isolation should be considered in immunosuppressed HD patients. Studies on shedding of viable SARS-CoV-2 are warranted in immunocompromised HD patients to inform policies regarding isolation and contact tracing protocols, and vaccination strategies.

19.
Journal of the American Society of Nephrology ; 33:47, 2022.
Article in English | EMBASE | ID: covidwho-2125896

ABSTRACT

Background: The administration of modified immune cells (MIC) prior to kidney transplantation led to specific immunosuppression against the allogeneic donor and a significant increase in regulatory B lymphocytes (Breg) (Morath et al., J Clin Invest 2020). We now wanted to investigate how this approach affects the clinical course of treated patients. Method(s): Clinical results of ten patients from a phase I clinical trial who had received MIC infusions before kidney transplantation were compared to results of 15 matched standard-risk recipients. Follow-up was until year five after surgery. Result(s): The 10 MIC patients had an excellent clinical course with stable kidney graft function and showed no donor-specific human leukocyte antigen antibodies (DSA) or acute rejections during follow-up. In contrast, 1 of 15 controls died and 5 of 15 controls developed DSA (log rank P = 0.046) (Figure 1 A, B). While the number of patients with a non-opportunistic infection did not differ significantly between groups (P = 0.36), opportunistic infections were reported more frequently in controls (log rank P = 0.033) (Figure 1 C). Compared to controls, MIC patients were found to have a trend towards a higher COVID-19 anti-S1 IgG index after vaccination with a median of 53 vs. 2 (P = 0.16). Importantly, the four MIC patients who had received the highest MIC cell dose 7 days before surgery and were on low immunosuppression during follow-up, continued to show absent anti-donor T lymphocyte reactivity in vitro and high CD19+CD24hiCD38hi transitional Breg as well as CD19+CD24hiCD27+ memory Breg. Conclusion(s): MIC infusions together with reduced conventional immunosuppression were associated with lower de novo DSA development and lower rates of opportunistic infections. In the future, MIC infusions could contribute to graft protection while reducing the side effects of immunosuppressive therapy. (Figure Presented).

20.
Journal of the American Society of Nephrology ; 33:483, 2022.
Article in English | EMBASE | ID: covidwho-2125786

ABSTRACT

Background: The PEXIVAS trial (2018) showed no outcome benefit with the routine use of plasma-exchange (PLEX) in patients with ANCA vasculitis and eGFR < 50mL/min. As a result, our clinical practice changed in favour of no PLEX and replacing a standard steroid wean with a fast steroid taper, thus altering the burden of immunosuppression in patients with ANCA vasculitis. We performed a retrospective analysis of a cohort of patients with ANCA vasculitis and renal involvement to determine whether this change in management impacted on patient outcomes and infections requiring hospitalisation. Method(s): We audited a cohort of ANCA vasculitis patients with renal involvement under follow-up at a tertiary centre diagnosed in the last 20 years. We collected demographic and clinical data including induction agent, PLEX regimen, and details of infections due to immunosuppression. The outcomes measured were patients who were in remission at one year and infections that required hospitalisation or CMV viraemia within 1 year of diagnosis Results: A total of 134 patients were identified, 91 diagnosed pre-PEXIVAS and 43 post-PEXIVAS. 6 patients died from COVID-19 by 1 year in the post-PEXIVAS group, these patients were excluded from analysis. Pre- and post-PEXIVAS mean age (60.6 yrs and 59 yrs respectively) and sex ratio (54/91 (59%) and 24/43 (55%)) were similar. The preferred induction agent pre-PEXIVAS was cyclophosphamide (65/91 (75%)) whilst there was a move to Rituximab in the post-PEXIVAS cohort(13/43 (48%)). Pre-PEXIVAS, 27/91 (29%) patients underwent PLEX versus 2/43 (4%) post-PEXIVAS. Remission rates at 1 year after diagnosis were similar between the two cohorts (pre: 65/91 (71.4%);post: 23/37 (53%);p=0.18 by Fisher's exact test). Infections that required hospitalisation were not significantly different but there was a trend to lower rate of admissions (pre: 16/91 (17.6%);post: 5/37 (12.2%);p=0.61 by Fisher's exact test). Conclusion(s): Our results suggest that change in clinical management after PEXIVAS was not associated with poorer outcomes in relation to treatment response and there was no significant difference in infections requiring hospitalisation at 1 year in patients with ANCA vasculitis. Our work complements recent findings that PLEX was not associated with improved rates of renal replacement therapy or mortality (Nezam et al. 2022).

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