Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience.

BACKGROUND: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft. METHODS: We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function. RESULTS: There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m 2 . Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases. CONCLUSIONS: The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients.

Seroprevalence and kinetics of SARS-CoV-2 antibodies in children in the UK: A prospective multicentre cohort study

BackgroundDuring the first wave of the SARS- CoV-2 pandemic in England, children accounted for just 1% of confirmed infections, had a milder clinical course and had much lower mortality than adults, a pattern similar to other international settings. The proportion of children in the UK infected with SARS-CoV-2 was unknown, with children less likely to attend symptomatic testing and issues with the sensitivity of real time reverse transcription PCR of oral/nasal swabs.ObjectivesTo measure the seroprevalence of SARS-CoV-2 antibodies in children of healthcare workers in the UK and to characterise the antibody response to SARS-CoV-2 infection and longitudinal antibody kinetics of SARS-CoV-2 infection.MethodsMulticentre observational prospective cohort study designed to determine seroprevalence of antibodies to SARS-CoV-2 in healthy children and report on symptoms experienced. Children of healthcare workers were recruited from five UK centres and underwent phlebotomy at three time points, beginning 16 April. There were follow up plasma/serum collections at two and six months after the original collection. Serum and/or plasma were tested for SARS-CoV-2 antibodies.Results1042 potential participants were screened for inclusion, with 35 excluded. Of the 1002 included 15 were excluded from analysis due to unsuccessful phlebotomy. Of the 992 included participants at the first time point, 68 had positive SARS-CoV-2 antibody tests, giving a seroprevalence of 6.9% (95% CI 5.4% to 8.6% n=992). Belfast had a significantly lower seroprevalence than all other sites at 0.9% (95% CI 0.2% to 3.3%, n=215, p<0.0001), and London had a seroprevalence significantly higher.849 of the 992 participants in the first round returned (86%). The median time between initial and follow up collections was 62 days. Of the 849 participants, 65 had positive SARS-CoV-2 antibody tests (7.66% CI 6.05–9.64). Of the 45 participants with positive antibody tests in the first round who attended the follow-up visit mean antibody titres increased. With Roche’s Elecsys assay, mean antibody titres increased from 84.7 cutoff index (COI) to 115.8 COI (difference 31.08, 95% CI 13.82–48.34, p=0.0007) and with DiaSorin’s LIAISON assay. mean antibody titres increased from 67.5 AU/ml to 81.4 AU/ml (13.89, 0.31–27.46;p=0.0452).Table summarising seroprevalence by site.Site Round 1(Number Reactive) Round 2(Number Reactive) First round Percentage Reactive (95% CI) Second Round Percentage Reactive (95%CI) All 992(77) 849(65) 7.76(6.26–9.59) 7.66(6.05,9.64) London 199(26) 135(20) 13.07(9.07,18.46) 14.81(9.8,21.78) Belfast 215(6) 200(4) 2.79(1.29,5.95) 2(0.78,5.03) Cardiff 178(10) 134(7) 5.613(3.08,10.03) 5.22(2.55, 10.39) Glasgow 224(20) 210(19) 8.93(5.85,13.39) 9.05(5.87, 13.7) Manchester 176(15) 170(15) 8.52(5.23,13.58) 9.82(5.42,14.05) The samples collected from the six month time point are still being processed, and results of antibody seroprevalence and antibody titre levels from this timepoint will be available before June.ConclusionsThe seroprevalence of SARS-CoV-2 antibodies amongst children of healthcare workers following the first wave in the UK was 6.9%, which was similar to the seroprevalence reported for adults in the UK at that time, and to international reports.The results from the second time point indicate that antibody titres in children infected with SARS-CoV-2 remain detectable for at least 62 days and indeed in this cohort increased.

Seroprevalence of SARS-CoV-2 antibodies in children of United Kingdom healthcare workers: a prospective multicentre cohort study protocol.

BACKGROUND: A novel coronavirus SARS-CoV-2 has been responsible for a worldwide pandemic. Children typically have very mild, or no, symptoms of infection. This makes estimations of seroprevalence in children difficult. Research is therefore required to determine the seroprevalence of SARS-CoV-2 antibodies in children. The primary objective of this study is to report the seroprevalence of SARS-CoV-2 IgM and/or IgG antibodies in healthy children at baseline, 2 months and 6 months. This is the only longitudinal UK study of seroprevalence in an exclusively paediatric population. Determining the changing seroprevalence is of vital public health importance and can help inform decisions around the lifting of paediatric specific social distancing measures such as school closures and the cancellation of routine paediatric hospital services. METHODS AND ANALYSIS: 1000 healthy children of healthcare workers aged between 2 and 15 years will be recruited from five UK sites (Belfast, Cardiff, Glasgow, London and Manchester). The children will undergo phlebotomy at baseline, 2 months and 6 months to measure IgM and/or IgG positivity to SARS-CoV-2. A sample size of 675 patients is required to detect a 5% change in seroprevalence at each time point assuming an alpha of 0.05 and a beta of 0.2. Adjusted probabilities for the presence of IgG and/or IgM antibodies and of SARS-CoV-2 infection will be reported using logistic regression models where appropriate. ETHICS AND DISSEMINATION: Ethical approval was obtained from the London - Chelsea Research Ethics Committee (REC Reference-20/HRA/1731) and the Belfast Health & Social Care Trust Research Governance (Reference 19147TW-SW). Results of this study will be made available as preprints and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT0434740; Results.

Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study.

BACKGROUND: Studies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity, test timing and selection bias. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection. DESIGN: This multicentre observational cohort study, conducted between 16 April to 3 July 2020 at 5 UK sites, recruited children of healthcare workers, aged 2-15 years. Participants provided blood samples for SARS-CoV-2 antibody testing and data were gathered regarding unwell contacts and symptoms. RESULTS: 1007 participants were enrolled, and 992 were included in the final analysis. The median age of participants was 10·1 years. There were 68 (6.9%) participants with positive SARS-CoV-2 antibody tests indicative of previous SARS-CoV-2 infection. Of these, 34/68 (50%) reported no symptoms prior to testing. The presence of antibodies and the mean antibody titre was not influenced by age. Following multivariable analysis four independent variables were identified as significantly associated with SARS-CoV-2 seropositivity: known infected household contact OR=10.9 (95% CI 6.1 to 19.6); fatigue OR=16.8 (95% CI 5.5 to 51.9); gastrointestinal symptoms OR=6.6 (95% CI 3.0 to 13.8); and changes in sense of smell or taste OR=10.0 (95% CI 2.4 to 11.4). DISCUSSION: Children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. Fatigue, gastrointestinal symptoms and changes in sense of smell or taste were the symptoms most strongly associated with SARS-CoV-2 antibody positivity. TRIAL REGISTRATION NUMBER: NCT0434740.