Imperial College London

Prof Liz Lightstone

Faculty of MedicineDepartment of Immunology and Inflammation

Consul (clinical) for the Faculty of Medicine
 
 
 
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Contact

 

+44 (0)20 3313 3152l.lightstone Website CV

 
 
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Assistant

 

Miss Anjli Jagpal +44 (0)20 3313 3152

 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

203 results found

Thomson T, Prendecki M, Gleeson S, Martin P, Spensley K, De Aguiar RC, Sandhu B, Seneschall C, Gan J, Clarke CL, Lewis S, Pickard G, Thomas D, McAdoo SP, Lightstone L, Cox A, Kelleher P, Willicombe Met al., 2022, Immune responses following 3rd and 4th doses of heterologous and homologous COVID-19 vaccines in kidney transplant recipients, eClinicalMedicine, Vol: 53, Pages: 1-9, ISSN: 2589-5370

BackgroundSolid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. In this study, we report on immune responses to 3rd- (V3) and 4th- (V4) doses of heterologous and homologous vaccines in a kidney transplant population.MethodsWe undertook a single centre cohort study of 724 kidney transplant recipients prospectively screened for serological responses following 3 primary doses of a SARS-CoV2 vaccine. 322 patients were sampled post-V4 for anti-spike (anti-S), with 69 undergoing assessment of SARS-CoV-2 T-cell responses. All vaccine doses were received post-transplant, only mRNA vaccines were used for V3 and V4 dosing. All participants had serological testing performed post-V2 and at least once prior to their first dose of vaccine.Findings586/724 (80.9%) patients were infection-naïve post-V3; 141/2586 (24.1%) remained seronegative at 31 (21-51) days post-V3. Timing of vaccination in relation to transplantation, OR: 0.28 (0.15-0.54), p=0.0001; immunosuppression burden, OR: 0.22 (0.13-0.37), p<0.0001, and a diagnosis of diabetes, OR: 0.49 (0.32-0.75), p=0.001, remained independent risk factors for non-seroconversion. Seropositive patients post-V3 had greater anti-S if primed with BNT162b2 compared with ChAdOx1, p=0.001.Post-V4, 45/239 (18.8%) infection-naïve patients remained seronegative. De novo seroconversion post-V4 occurred in 15/60 (25.0%) patients. There was no difference in anti-S post-V4 by vaccine combination, p=0.50. T-cell responses were poor, with only 11/54 (20.4%) infection-naive patients having detectable T-cell responses post-V4, with no difference seen by vaccine type.InterpretationA significant proportion of transplant recipients remain seronegative following 3- and 4- doses of SARS-CoV-2 vaccines, with poor T-cell responses, and are likely to have inadequate protection against infection. As such alternative strategies are required to provide protection to this vulnerable group.FundingMW/PK received study

Journal article

Martin P, Gleeson S, Clarke C, Thomson T, Edwards H, Spensley K, Mortimer P, Mcintyre S, cox A, Pickard G, Lightstone E, Thomas D, McAdoo S, kelleher P, Prendecki M, Willicombe Met al., 2022, Comparison of immunogenicity and clinical effectiveness between BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines in people with end-stage kidney disease receiving haemodialysis: a prospective, observational cohort study, The Lancet Regional Health Europe, Vol: 21, ISSN: 2666-7762

Background:People with end-stage kidney disease, including people on haemodialysis, are susceptible to greater COVID-19 related morbidity and mortality. This study compares the immunogenicity and clinical effectiveness of BNT162B2 versus ChAdOx1 in haemodialysis patients.Methods:In this observational cohort study, 1021 patients were followed-up from time of vaccination until December 2021. All patients underwent weekly RT-PCR screening. Patients were assessed for nucleocapsid(anti-NP) and spike(anti-S) antibodies at timepoints after second(V2) and third(V3) vaccinations. 191 patients were investigated for T-cell responses. Vaccine effectiveness (VE) for prevention of infection, hospitalisation and mortality was evaluated using the formula VE=(1-adjustedHR)x100.Findings:45.7% (467/1021) had evidence of prior infection. There was no difference in the proportion of infection-naïve patients who seroconverted by vaccine type, but median anti-S antibody titres were higher post-BNT162b2 compared with ChAdOx1; 462(152-1171) and 78(20-213) BAU/ml respectively, p<0.001. Concomitant immunosuppressant use was a risk factor for non-response, OR 0.12[95% CI 0.05–0.25] p<0.001. Post-V3 (all BNT162b2), median anti-S antibody titres remained higher in those receiving BNT162b2 versus ChAdOx1 as primary doses; 2756(187–1246) and 1250(439–2635) BAU/ml respectively, p=0.003.Anti-S antibodies waned over time. Hierarchical levels of anti-S post-V2 predicted risk of infection; patients with no/low anti-S being at highest risk. VE for preventing infection, hospitalisation and death was 53% (95% CI 6–75), 77% (95% CI 30–92) and 93% (95% CI 59–99) respectively, with no difference seen by vaccine type.Interpretation:Serum anti-S concentrations predict risk of breakthrough infection. Anti-S responses vary dependent upon clinical features, infection history and vaccine type. Monitoring of serological responses may enable individualised approaches

Journal article

Evans RA, Leavy OC, Richardson M, Elneima O, McCauley HJC, Shikotra A, Singapuri A, Sereno M, Saunders RM, Harris VC, Houchen-Wolloff L, Aul R, Beirne P, Bolton CE, Brown JS, Choudhury G, Diar-Bakerly N, Easom N, Echevarria C, Fuld J, Hart N, Hurst J, Jones MG, Parekh D, Pfeffer P, Rahman NM, Rowland-Jones SL, Shah AM, Wootton DG, Chalder T, Davies MJ, De Soyza A, Geddes JR, Greenhalf W, Greening NJ, Heaney LG, Heller S, Howard LS, Jacob J, Jenkins RG, Lord JM, Man WD-C, McCann GP, Neubauer S, Openshaw PJM, Porter JC, Rowland MJ, Scott JT, Semple MG, Singh SJ, Thomas DC, Toshner M, Lewis KE, Thwaites RS, Briggs A, Docherty AB, Kerr S, Lone NI, Quint J, Sheikh A, Thorpe M, Zheng B, Chalmers JD, Ho LP, Horsley A, Marks M, Poinasamy K, Raman B, Harrison EM, Wain LV, Brightling CE, Abel K, Adamali H, Adeloye D, Adeyemi O, Adrego R, Aguilar Jimenez LA, Ahmad S, Ahmad Haider N, Ahmed R, Ahwireng N, Ainsworth M, Al-Sheklly B, Alamoudi A, Ali M, Aljaroof M, All AM, Allan L, Allen RJ, Allerton L, Allsop L, Almeida P, Altmann D, Alvarez Corral M, Amoils S, Anderson D, Antoniades C, Arbane G, Arias A, Armour C, Armstrong L, Armstrong N, Arnold D, Arnold H, Ashish A, Ashworth A, Ashworth M, Aslani S, Assefa-Kebede H, Atkin C, Atkin P, Aung H, Austin L, Avram C, Ayoub A, Babores M, Baggott R, Bagshaw J, Baguley D, Bailey L, Baillie JK, Bain S, Bakali M, Bakau M, Baldry E, Baldwin D, Ballard C, Banerjee A, Bang B, Barker RE, Barman L, Barratt S, Barrett F, Basire D, Basu N, Bates M, Bates A, Batterham R, Baxendale H, Bayes H, Beadsworth M, Beckett P, Beggs M, Begum M, Bell D, Bell R, Bennett K, Beranova E, Bermperi A, Berridge A, Berry C, Betts S, Bevan E, Bhui K, Bingham M, Birchall K, Bishop L, Bisnauthsing K, Blaikely J, Bloss A, Bolger A, Bonnington J, Botkai A, Bourne C, Bourne M, Bramham K, Brear L, Breen G, Breeze J, Bright E, Brill S, Brindle K, Broad L, Broadley A, Brookes C, Broome M, Brown A, Brown A, Brown J, Brown J, Brown M, Brown M, Brown V, Brugha T, Brunskill Net al., 2022, Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study, The Lancet Respiratory Medicine, Vol: 10, Pages: 761-775, ISSN: 2213-2600

BackgroundNo effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.MethodsThe Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.Findings2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obes

Journal article

Gleeson S, Lightstone L, 2022, BLISS-LN trial revisited: function matters (vol 101, pg 224, 2022), KIDNEY INTERNATIONAL, Vol: 101, Pages: 1302-1302, ISSN: 0085-2538

Journal article

Spensley K, Gleeson S, Martin P, Thomson T, Clarke C, Pickard G, Thomas D, McAdoo S, Randell P, Kelleher P, Bedi R, Lightstone E, Prendecki M, Willicombe Met al., 2022, Comparison of vaccine effectiveness against the Omicron (B.1.1.529) variant in haemodialysis patients, Kidney International Reports, Vol: 7, Pages: 1406-1409, ISSN: 2468-0249

Journal article

Jesudason S, Hewawasam E, Moloney B, Tan R, Li J, Blakey H, Bramham K, Hall M, Juneja R, Jarvis E, Lightstone L, Lipkin G, Hladunewich MAet al., 2022, Comparison of catheters or new arteriovenous fistulas for commencement of haemodialysis in pregnant women with chronic kidney disease: an international observational study, JOURNAL OF NEPHROLOGY, Vol: 35, Pages: 1689-1698, ISSN: 1121-8428

Journal article

Turner-Stokes T, Edwards H, Lightstone L, 2022, COVID-19 in patients with glomerular disease., Current Opinion in Nephrology and Hypertension, Vol: 31, Pages: 191-198, ISSN: 1062-4821

PURPOSE OF REVIEW: Managing patients with glomerular disease during the COVID-19 pandemic has been challenging, as the infection risk associated with immunosuppression must be balanced against the need to control severe glomerular disease that can lead to kidney failure. This review provides an overview of COVID-19 and the effectiveness of SARS-CoV-2 vaccination in patients with glomerular disease. RECENT FINDINGS: Registry data, although biased towards outcomes of hospitalized patients, suggest that the mortality from COVID-19 is higher in patients with glomerular disease than in the general population. Glucocorticoid use prior to SARS-CoV-2 infection is associated with adverse outcomes from COVID-19. Rituximab significantly attenuates serological responses to both natural infection and vaccination against SARS-CoV-2, although it is not clear whether this leads to adverse outcomes. Case reports of disease flares occurring after vaccination have been reported, but causality in any of these cases has yet to be proven and the absolute risk remains very small. SUMMARY: Patients with glomerular disease represent an at-risk group for severe COVID-19 disease and vaccination is key to reducing this risk. As immunosuppressed patients demonstrate an attenuated response to vaccination, the efficacy of a third primary dose followed by a subsequent booster is being investigated.

Journal article

Beckwith H, Lightstone L, McAdoo S, 2022, Sex and gender in glomerular disease., Seminars in Nephrology, Vol: 42, Pages: 185-196, ISSN: 0270-9295

There is increasing understanding that a multifaceted interplay of sex-dependent genetic and immune dysregulation underpins the development of glomerular disorders. Regional and ethnic variations in glomerular disease incidence make delineating the effects of sex and gender on disease pathophysiology more complex, but there is a marked paucity of research in this area. This review article presents a summary of the current understanding of sex and gender in glomerular disease, highlighting the broader effects of sex and gender on autoimmunity, clinical presentations, and pathophysiology of individual glomerular diseases, as well as exploring sex, gender, and glomerular disease within a wider socioenvironmental context. It is important to specifically consider the effects of sex and gender when presenting and analyzing clinical and scientific studies on glomerular disease. Failure to do so risks promoting disparities within health care provision, neglecting opportunities to identify sex-specific biomarkers, and potentially hindering the development of sex-specific therapies.

Journal article

Waldman M, Soler MJ, García-Carro C, Lightstone L, Turner-Stokes T, Griffith M, Torras J, Martinez Valenzuela L, Bestard O, Geddes C, Flossmann O, Budge KL, Cantarelli C, Fiaccadori E, Delsante M, Morales E, Gutierrez E, Niño-Cruz JA, Martinez-Rueda AJ, Comai G, Bini C, La Manna G, Slon MF, Manrique J, Avello A, Fernandez-Prado R, Ortiz A, Marinaki S, Martin Varas CR, Rabasco Ruiz C, Sierra-Carpio M, García-Agudo R, Fernández Juárez G, Hamilton AJ, Bruchfeld A, Chrysochou C, Howard L, Sinha S, Leach T, Agraz Pamplona I, Maggiore U, Cravedi Pet al., 2022, COVID-19 in Patients with Glomerular Disease: Follow-Up Results from the IRoc-GN International Registry., Kidney360, Vol: 3, Pages: 293-306

BACKGROUND: The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN. METHODS: We collected serial information on kidney-related and -unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3-9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use. RESULTS: After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P=0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; P<0.001). GN patients developing AKI were less likely to recover pre-COVID-19 eGFR compared with controls (adjusted 6-month post-COVID-19 eGFR=0.41; 95% CI, 0.25 to 0.56; times pre-COVID-19 eGFR). Shorter duration of GN diagnosis, higher pre-COVID-19 proteinuria, and diagnosis of focal segmental glomerulosclerosis or minimal change disease were associated with a lower post-COVID-19 eGFR. CONCLUSIONS: Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution.

Journal article

Gleeson S, Lightstone L, 2022, BLISS-LN trial revisited: function matters, KIDNEY INTERNATIONAL, Vol: 101, Pages: 224-226, ISSN: 0085-2538

Journal article

Gilmore A, Wilson H, Cairns T, Botto M, Lightstone L, Bruce I, Cook H, Pickering M, on behalf of the MASTERPLANS Consortiumet al., 2022, Immune gene expression and functional networks in distinct lupus nephritis classes, Lupus Science & Medicine, Vol: 9, ISSN: 2053-8790

Objective: To explore the utility of the NanoString platform in elucidating kidney immune transcripts for class III, IV and V lupus nephritis (LN) using a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) kidney biopsy tissue.Methods: Immune gene transcript analysis was performed using the NanoString nCounter platform on RNA from LN (n=55), thin basement membrane disease (TBM, n=14) and membranous nephropathy (MN, n=9) FFPE kidney biopsy tissue. LN samples consisted of single class III (n=11), IV (n=23) and V (n=21) biopsies with no mixed lesions. Differential gene expression was performed with NanoString nSolver, with visualisations of volcano plots and heatmaps generated in R. Significant transcripts were interrogated to identify functional networks using STRING and Gene ontogeny terms. Results: In comparison to TBM, we identified 52 significantly differentially expressed genes common to all three LN classes. Pathway analysis showed enrichment for type I interferon (IFN) signalling, complement and MHC II pathways, with most showing the highest expression in class IV LN. Our class IV LN biopsies also showed significant upregulation of NF-κB signalling and immunological enrichment in comparison to class V LN biopsies. Transcripts from the type I IFN pathway distinguished class V LN from MN. Conclusion: Our whole kidney section transcriptomic analysis provided insights into the molecular profile of class III, IV and V LN. The data highlighted important pathways common to all three classes and pathways enriched in our class IV LN biopsies. The ability to reveal molecular pathways in LN using FFPE whole biopsy sections could have clinical utility in treatment selection for LN.

Journal article

Greenhalgh T, Griffin S, Gurdasani D, Hamdy A, Katzourakis A, McKee M, Michie S, Pagel C, Roberts A, Yates K, Alwan N, Agius R, Ahmed H, Ashworth S, Augst C, Bacon SL, Bergholtz EJ, Blanchflower D, Bosman A, Ben Alaya NBE, Brown K, Butler M, Byrne M, Cacciola R, Cane DJ, Cascini F, Chahed M, Cheng KK, Costello A, Morris AC, Davies R, Davis C, Delaney B, Dewald D, Drew D, Ewing A, Drury J, Fisman D, Friel S, Gasperowicz M, Grimes DR, Haque Z, Haseltine WA, Hegarty O, Hodes S, Hughes E, Hyde Z, Iannattone L, Jadad AR, Jha N, Jimenez JL, Jimenez JL, Johnson J, Karan A, Khunti K, Khuri-Bulos N, Kim WJ, Knight MJ, Lavoie KL, Lawton T, Lazarus JV, Leonardi AJ, Leshem E, Lightstone L, Markov PV, Martin-Moreno JM, Meier P, Mesiano-Crookston J, Mishra AK, Moore M, Moschos SA, Naylor CD, Nichols T, Nicholl D, Norheim OF, Oliver M, Peters C, Pillay D, Pimenta D, Pirzada K, Pope C, Prather KA, Preest G, Quereshi Z, Rabiei K, Ray J, Reddy KS, Ricciardi W, Rice K, Robertson E, Roberts K, Ryan T, Salisbury H, Scally G, Schooley RT, Shah V, Silver J, Silvey N, Sivan M, Souza LE, Staines A, Tomlinson D, Tukuitonga C, Vincent C, Vipond J, West R, Weyand AC, Ziauddeen Het al., 2022, Covid-19: An urgent call for global "vaccines-plus" action, BMJ-BRITISH MEDICAL JOURNAL, Vol: 376, ISSN: 0959-535X

Journal article

Podos S, Nester C, Appel G, Bomback A, Bouman KP, Cook T, Daina E, Dixon B, Langman C, Lightstone L, Thanassi J, Rice K, Huang M, Parikh SV, Pickering M, Sperati J, Trachtman H, Tumlin J, Wetzels J, Remuzzi Get al., 2022, Clinical and biomarker characteristics of patients with C3G enrolled in two phase II studies investigating the factor D inhibitor danicopan, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 148-148, ISSN: 0161-5890

Conference paper

Carter SA, Teng C, Gutman T, Logeman C, Cattran D, Lightstone L, Bagga A, Barbour SJ, Barratt J, Boletis J, Caster DJ, Coppo R, Fervenza FC, Floege J, Hladunewich MA, Hogan JJ, Kitching AR, Lafayette RA, Malvar A, Radhakrishnan J, Rovin BH, Scholes-Robertson N, Trimarchi H, Zhang H, Azukaitis K, Cho Y, Viecelli AK, Dunn L, Harris D, Johnson DW, Kerr PG, Laboi P, Ryan J, Shen J, Ruiz L, Wang AY-M, Lee AHK, Shun SFK, Tong MK-H, Teixeira-Pinto A, Wilkie M, Alexander S, Craig JC, Martin A, Tong Aet al., 2021, A Focus Group Study of Self-Management in Patients With Glomerular Disease, KIDNEY INTERNATIONAL REPORTS, Vol: 7, Pages: 56-67, ISSN: 2468-0249

Journal article

Carter SA, Lightstone L, Cattran D, Tong A, Bagga A, Barbour SJ, Barratt J, Boletis J, Caster DJ, Coppo R, Fervenza FC, Floege J, Hladunewich MA, Hogan JJ, Kitching AR, Lafayette RA, Malvar A, Radhakrishnan J, Rovin BH, Scholes-Robertson N, Trimarchi H, Zhang H, Anumudu S, Cho Y, Gutman T, O'Lone E, Viecelli AK, Au E, Azukaitis K, Baumgart A, Bernier-Jean A, Dunn L, Howell M, Ju A, Logeman C, Nataatmadja M, Sautenet B, Sharma A, Craig JCet al., 2021, A Core Outcome Set for Trials in Glomerular Disease A Report of the Standardized Outcomes in Nephrology?Glomerular Disease (SONG-GD) Stakeholder Workshops, CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 17, Pages: 53-64, ISSN: 1555-9041

Journal article

Wiles K, Webster P, Seed PT, Bennett-Richards K, Bramham K, Brunskill N, Carr S, Hall M, Khan R, Nelson-Piercy C, Webster LM, Chappell LC, Lightstone Let al., 2021, The impact of chronic kidney disease Stages 3-5 on pregnancy outcomes, NEPHROLOGY DIALYSIS TRANSPLANTATION, Vol: 36, Pages: 2008-2017, ISSN: 0931-0509

Journal article

Shipa M, Embleton-Thirsk A, Parvaz M, Santos LR, Muller P, Chowdhury K, Isenberg DA, Dore CJ, Gordon C, Ehrenstein MRet al., 2021, Effectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus A Randomized Controlled Trial, ANNALS OF INTERNAL MEDICINE, Vol: 174, Pages: 1647-+, ISSN: 0003-4819

Journal article

Prendecki M, Thomson T, Clarke CL, Martin P, Gleeson S, De Aguiar RC, Edwards H, Mortimer P, McIntyre S, Mokreri D, Cox A, Pickard G, Lightstone L, Thomas D, McAdoo SP, Kelleher P, Willicombe Met al., 2021, responses to SARS-CoV-2 vaccines in kidney transplant recipients, LANCET, Vol: 398, Pages: 1482-1484, ISSN: 0140-6736

Journal article

Evans RA, McAuley H, Harrison EM, Shikotra A, Singapuri A, Sereno M, Elneima O, Docherty AB, Lone NI, Leavy OC, Daines L, Baillie JK, Brown JS, Chalder T, De Soyza A, Diar Bakerly N, Easom N, Geddes JR, Greening NJ, Hart N, Heaney LG, Heller S, Howard L, Hurst JR, Jacob J, Jenkins RG, Jolley C, Kerr S, Kon OM, Lewis K, Lord JM, McCann GP, Neubauer S, Openshaw PJM, Parekh D, Pfeffer P, Rahman NM, Raman B, Richardson M, Rowland M, Semple MG, Shah AM, Singh SJ, Sheikh A, Thomas D, Toshner M, Chalmers JD, Ho L-P, Horsley A, Marks M, Poinasamy K, Wain LV, Brightling CE, PHOSP-COVID Collaborative Groupet al., 2021, Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study, The Lancet Respiratory Medicine, Vol: 9, Pages: 1275-1287, ISSN: 2213-2600

BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health bur

Journal article

Carter SA, Logeman C, Howell M, Cattran D, Lightstone L, Bagga A, Barbour SJ, Barratt J, Boletis J, Caster DJ, Coppo R, Fervenza FC, Floege J, Hladunewich MA, Hogan JJ, Kitching AR, Lafayette RA, Malvar A, Radhakrishnan J, Rovin BH, Scholes-Robertson N, Trimarchi H, Zhang H, Cho Y, Dunn L, Gipson DS, Liew A, Sautenet B, Viecelli AK, Harris D, Johnson DW, Wang AY-M, Teixeira-Pinto A, Alexander SI, Martin A, Tong A, Craig JCet al., 2021, Development of an international Delphi survey to establish core outcome domains for trials in adults with glomerular disease, KIDNEY INTERNATIONAL, Vol: 100, Pages: 881-893, ISSN: 0085-2538

Journal article

Furie R, Houssiau F, Lightstone L, Yu X, Weinmann-Menke J, Tanaka Y, Jones-Leone A, Gonzalez-Rivera T, Gilbride J, Madan A, Green Y, Roth Det al., 2021, Belimumab Improves Renal Responses in Patients with or Without Steroid Pulses During Induction Therapy for Lupus Nephritis, Publisher: WILEY, Pages: 3068-3070, ISSN: 2326-5191

Conference paper

Prendecki M, Clarke C, Edwards H, McIntyre S, Mortimer P, Gleeson S, Martin P, Thomson T, Randell P, Shah A, Singanayagam A, Lightstone L, Cox A, Kelleher P, Willicombe M, McAdoo SPet al., 2021, Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression., Annals of the Rheumatic Diseases, Vol: 80, Pages: 1322-1329, ISSN: 0003-4967

OBJECTIVE: There is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination. METHODS: Serological and T-cell ELISpot assays were used to assess the response to first-dose and second-dose SARS-CoV-2 vaccine (with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccines) in 140 participants receiving immunosuppression for autoimmune rheumatic and glomerular diseases. RESULTS: Following first-dose vaccine, 28.6% (34/119) of infection-naïve participants seroconverted and 26.0% (13/50) had detectable T-cell responses to SARS-CoV-2. Immune responses were augmented by second-dose vaccine, increasing seroconversion and T-cell response rates to 59.3% (54/91) and 82.6% (38/46), respectively. B-cell depletion at the time of vaccination was associated with failure to seroconvert, and tacrolimus therapy was associated with diminished T-cell responses. Reassuringly, only 8.7% of infection-naïve patients had neither antibody nor T-cell responses detected following second-dose vaccine. In patients with evidence of prior SARS-CoV-2 infection (19/140), all mounted high-titre antibody responses after first-dose vaccine, regardless of immunosuppressive therapy. CONCLUSION: SARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppression, when assessed by a combination of serology and cell-based assays, although the response is impaired compared with healthy individuals. B-cell depletion following rituximab impairs serological responses, but T-cell responses are preserved in this group. We suggest that repeat vaccine doses for serological non-responders should be investigated as means to induce more robust immunological response.

Journal article

Ralston E, Bramham K, Clery A, Wang Y, Wiles K, Blakey H, Lipkin G, Hall M, Lightstone L, Chappell L, Webster P, Carr Set al., 2021, Pregnancy-associated progression of chronic kidney disease: development of a clinical predictive tool, Publisher: WILEY, Pages: E36-E36, ISSN: 1470-0328

Conference paper

Clarke CL, Prendecki M, Dhutia A, Gan J, Edwards C, Prout V, Lightstone L, Parker E, Marchesin F, Griffith M, Charif R, Pickard G, Cox A, McClure M, Tedder R, Randell P, Greathead L, Guckian M, McAdoo SP, Kelleher P, Willicombe Met al., 2021, Longevity of SARS-CoV-2 immune responses in hemodialysis patients and protection against reinfection, Kidney International, Vol: 99, Pages: 1470-1477, ISSN: 0085-2538

Patients with end stage kidney disease receiving in-center hemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, patients receiving ICHD frequently develop circulating antibodies to SARS-CoV-2, even with asymptomatic infection. Here, we investigated the durability and functionality of the immune responses to SARS-CoV-2 infection in patients receiving ICHD. Three hundred and fifty-six such patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection. Patients were regularly screened for nucleocapsid protein (anti-NP) and receptor binding domain (anti-RBD) antibodies, and those who became seronegative at six months were screened for SARS-CoV-2 specific T-cell responses. One hundred and twenty-nine (36.2%) patients had detectable antibody to anti-NP at time zero, of whom 127 also had detectable anti-RBD. Significantly, at six months, 71/111 (64.0%) and 99/116 (85.3%) remained anti-NP and anti-RBD seropositive, respectively. For patients who retained antibody, both anti-NP and anti-RBD levels were reduced significantly after six months. Eleven patients who were anti-NP seropositive at time zero, had no detectable antibody at six months; of whom eight were found to have SARS-CoV-2 antigen specific T cell responses. Independent of antibody status at six months, patients with baseline positive SARS-CoV-2 serology were significantly less likely to have PCR confirmed infection over the following six months. Thus, patients receiving ICHD mount durable immune responses six months post SARS-CoV-2 infection, with fewer than 3% of patients showing no evidence of humoral or cellular immunity.

Journal article

Satta G, Youngstein T, Lightstone L, Gilchrist M, COVID-19 treatment guidelines working group at Imperial College Healthcare NHS Trustet al., 2021, The utility of a local multidisciplinary working group to oversee the establishment of rapidly evolving standards of care and to support trial recruitment during the COVID-19 pandemic, Clinical medicine (London, England), Vol: 21, Pages: e287-e289, ISSN: 1470-2118

Coronavirus disease 2019 (COVID-19) was first identified in December 2019 in Wuhan, China. The first analyses of cases described high numbers of critically ill patients requiring intensive care admission with significant late inflammatory features. By the time the first cases of SARS-CoV-2 infection were diagnosed in the UK, a wide range of drugs were under consideration and it became clear that the input of clinicians covering all organ systems (in particular, infectious diseases, haematology, rheumatology, renal medicine and intensive care) and of expert specialist pharmacists was necessary at the local level. Thus, an expert multidisciplinary (MDT) group within our organisation was convened to offer a standardised approach and robust clinical governance for the treatment of COVID-19 patients admitted to our hospitals and rapidly develop standards of care as evidence evolved. This commentary explores the methods and mechanisms for creating an MDT COVID-19 treatment working group which are applicable to any hospital likely to admit and care for high numbers of COVID-19 patients and demonstrates how the structure and governance of the group allowed for rapid adoption of both dexamethasone and tocilizumab into standard of care as data became available.

Journal article

Nester C, Podos S, Hogan J, Appel G, Bomback A, Bouman K, Cook T, Daina E, Dixon B, Langman C, Lightstone L, Thanassi J, Rice K, Huang M, Parikh S, Pickering M, Sperati J, Trachtman H, Tumlin J, Wetzels JFM, Remuzzi Get al., 2021, CLINICAL AND BIOMARKER CHARACTERISTICS OF PATIENTS WITH C3G OR IC-MPGN ENROLLED IN TWO PHASE II STUDIES INVESTIGATING THE FACTOR D INHIBITOR DANICOPAN, 58th Congress of the European-Renal-Association (ERA)-European-Dialysis-and-Transplant-Association (EDTA), Publisher: OXFORD UNIV PRESS, Pages: 149-149, ISSN: 0931-0509

Conference paper

Gleeson S, Martin P, Bedi R, Lynch K, Willicombe M, Lightstone Let al., 2021, Answering the call to action: rapid implementation of an in-center hemodialysis SARS-CoV-2 vaccination program, Kidney International, Vol: 99, Pages: 1238-1239, ISSN: 0085-2538

Journal article

Turner-Stokes T, Jiang E, Johnson N, Khakhria K, Kong E, Cairns T, Clarke C, Greathead L, Griffith M, Guckian M, Kelleher P, McClure MO, Prendecki M, Rosadas C, Tedder R, Lightstone L, Willicombe M, McAdoo SP, ICHNT Renal COVID-19 Groupet al., 2021, Serological screening for COVID-19 in patients with glomerular disease, Kidney International Reports, Vol: 6, Pages: 1402-1406, ISSN: 2468-0249

Journal article

Medjeral-Thomas N, Troldborg A, Hansen A, Gisby J, Clarke C, Prendecki M, McAdoo S, Sandhu E, Lightstone E, Thomas D, Willicombe M, Botto M, Peters J, Pickering M, Thiel Set al., 2021, Plasma lectin pathway complement proteins in patients with COVID-19 and renal disease, Frontiers in Immunology, Vol: 12, ISSN: 1664-3224

We do not understand why non-white ethnicity and chronic kidney disease increase susceptibility to COVID-19. The lectin pathway of complement activation is a key contributor to innate immunity and inflammation. Concentrations of plasma lectin pathway proteins influence pathway activity and vary with ethnicity. We measured circulating lectin proteins in a multi-ethnic cohort of chronic kidney disease patients with and without COVID19 infection to determine if lectin pathway activation was contributing to COVID19 severity.We measured 11 lectin proteins in serial samples from a cohort of 33 patients with chronic kidney impairment and COVID19. Controls were single plasma samples from 32 patients on dialysis and 32 healthy individuals. We demonstrated multiple associations between recognition molecules and associated proteases of the lectin pathway and COVID-19, including COVID-19 severity. Some of these associations were unique to patients of Asian and White ethnicity. Our novel findings demonstrate that COVID19 infection alters the concentration of plasma lectin proteins and some of these changes were linked to ethnicity. This suggests a role for the lectin pathway in the host response to COVID-19 and suggest that variability within this pathway may contribute to ethnicity-associated differences in susceptibility to severe COVID-19.

Journal article

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