Imperial College London

ProfessorDannyAltmann

Faculty of MedicineDepartment of Immunology and Inflammation

Professor of Immunology
 
 
 
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Contact

 

+44 (0)20 3313 8212d.altmann

 
 
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Location

 

5S5CHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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270 results found

Lord JM, Veenith T, Sullivan J, Sharma-Oates A, Richter AG, Greening NJ, McAuley HJC, Evans RA, Moss P, Moore SC, Turtle L, Gautam N, Gilani A, Bajaj M, Wain LV, Brightling C, Raman B, Marks M, Singapuri A, Elneima O, Openshaw PJM, Duggal NA, PHOSP-COVID Study collaborative group, ISARIC4C investigatorset al., 2024, Accelarated immune ageing is associated with COVID-19 disease severity., Immun Ageing, Vol: 21, ISSN: 1742-4933

BACKGROUND: The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. RESULTS: We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3-5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28-ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 sur

Journal article

Liu Z, Alexander J, Eng K, Ibraheim H, Anandabaskaran S, Saifuddin M, Constable L, Castro Seoane R, Balarajah S, Hicks L, Williams H, Teare J, Altmann D, Boyton R, Pollock K, Hart A, Powell Net al., 2023, Antibody responses to Influenza vaccination are diminished in patients with inflammatory bowel disease on infliximab or tofacitinib, Journal of Crohn's and Colitis, ISSN: 1873-9946

Background and aims:We sought to determine whether six commonly used immunosuppressive regimens were associated with lower antibody responses after seasonal influenza vaccination in patients with IBD.Methods:We conducted a prospective study including 213 IBD patients and 53 healthy controls; 165 who had received seasonal influenza vaccine and 101 who had not. IBD medications included infliximab, thiopurines, infliximab and thiopurine combination therapy, ustekinumab, vedolizumab or tofacitinib. The primary outcome was antibody responses against influenza/A H3N2 and A/H1N1, compared to controls, adjusting for age, prior vaccination and interval between vaccination and sampling.Results:Lower antibody responses against influenza A/H3N2 were observed in patients on infliximab (Geometric Mean Ratio 0.35 [95% CI 0.20-0.60], p=0.0002), combination of infliximab and thiopurine therapy (0.46 [0.27-0.79], p=0.0050) and tofacitinib (0.28 [0.14-0.57], p=0.0005) compared to controls. Lower antibody responses against A/H1N1 were observed in patients on infliximab (0.29 [0.15-0.56], p=0.0003), combination of infliximab and thiopurine therapy (0.34 [0.17-0.66], p=0.0016), thiopurine monotherapy (0.46 [0.24-0.87], p=0.017) and tofacitinib (0.23 [0.10-0.56], p=0.0013). Ustekinumab and vedolizumab were not associated with reduced antibody responses against A/H3N2 or A/H1N1. Vaccination in the previous year was associated with higher antibody responses to A/H3N2. Vaccine-induced anti-SARS-CoV-2 antibody concentration weakly correlated with antibodies against H3N2 (r=0.27; p=0.0004) and H1N1 (r=0.33; p<0.0001).Conclusions:Vaccination in both the 2020-2021 and 2021-2022 seasons was associated with significantly higher antibody responses to influenza/A than no vaccination or vaccination in 2021-2022 alone. Infliximab and tofacitinib are associated with lower binding antibody responses to Influenza/A, similar to COVID-19 vaccine-induced antibody responses. Funding:Financial support was

Journal article

C-MOREPHOSP-COVID Collaborative Group, 2023, Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study, The Lancet Respiratory Medicine, Vol: 11, Pages: 1003-1019, ISSN: 2213-2600

INTRODUCTION: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. METHODS: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. FINDINGS: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MR

Journal article

Brightling CE, Evans RA, Singapuri A, Smith N, Wain LV, PHOSP-COVID Collaborative Groupet al., 2023, Long COVID research: an update from the PHOSP-COVID Scientific Summit., Lancet Respir Med, Vol: 11, Pages: e93-e94

Journal article

Altmann DM, Whettlock EM, Liu S, Arachchillage DJ, Boyton RJet al., 2023, The immunology of long COVID (vol 23, 618, 2023), NATURE REVIEWS IMMUNOLOGY, Vol: 23, Pages: 697-697, ISSN: 1474-1733

Journal article

Liu Z, Alexander J, Le K, Zhou X, Ibraheim H, Anandabaskaran S, Saifuddin M, LIN K, Leon M, Constable L, Castro Seoane R, Anand N, Bewshea C, Nice R, D'Mello A, Jones G, Balarajah S, Fiorentino F, Sebastian S, Irving P, Hicks LC, Williams HRT, Kent A, Linger R, Parkes M, Klaartje K, Patel K, Teare JP, Altmann DM, Boyton RJ, Hart AL, Lees C, Goodhand J, Kennedy N, Pollock K, Ahmad T, Powell Net al., 2023, Neutralising antibody responses against SARS-CoV-2 Omicron BA.4/5 and wild-type virus in patients with inflammatory bowel disease following three doses of COVID-19 vaccine (VIP): a prospective, multicentre, cohort study, EClinicalMedicine, Vol: 64, ISSN: 2589-5370

BackgroundPatients with inflammatory bowel disease (IBD) receiving anti-TNF and JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the Omicron BA.4/5 variant.MethodsIn this multicentre cohort study, we prospectively recruited 340 adults (69 healthy controls and 271 IBD) at nine UK hospitals between May 28, 2021 and March 29, 2022. The IBD study population was established (>12 weeks therapy) on either thiopurine (n = 63), infliximab (n = 45), thiopurine and infliximab combination therapy (n = 48), ustekinumab (n = 45), vedolizumab (n = 46) or tofacitinib (n = 24). Patients were excluded if they were being treated with any other immunosuppressive therapies. Participants had two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccines, followed by a third dose of either BNT162b2 or mRNA1273. Pseudo-neutralisation assays against SARS-CoV-2 wild-type and BA.4/5 were performed. The half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARS-CoV-2 neutralising response against wild-type virus and Omicron BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, vaccine type, age, and interval between vaccination and blood collection. This study is registered with ISRCTN (No. 13495664).FindingsBoth heterologous (first two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both wild-type SARS-CoV-2 virus and the Omicron BA.4/5 variant in healthy participants and patients with IBD. Antibody titres against BA.4/5 were significantly lower than antibodies against wild-type virus in both healthy participants and patients with IBD (p < 0.0001). Multivariable models demonstrated that neutralising antibodies against

Journal article

Salgado BB, Barbosa ARC, Arcanjo AR, de Castro DB, Ramos TCA, Naveca F, Altmann DM, Boyton RJ, Lalwani JDB, Lalwani Pet al., 2023, Hybrid immunity results in enhanced and more sustained antibody responses after the second Sinovac-Coronavac dose in a Brazilian cohort: DETECTCoV-19 cohort, Viruses, Vol: 15, ISSN: 1999-4915

We measured anti-SARS-CoV-2 antibody responses before and after CoronaVac (inactivated) vaccination in a case-control study performed in CoronaVac-immunized individuals participating in a longitudinal prospective study of adults in Manaus (DETECTCoV-19). Antibody responses were measured by standard serological immunoassays. Peak anti-S-RBD and neutralizing RBD-ACE2 blocking antibody responses after two doses of CoronaVac vaccine were similar in vaccine breakthrough cases (n = 9) and matched controls (n = 45). Individuals with hybrid immunity resulting from prior SARS-CoV-2 infection followed by vaccination (n = 22) had elevated levels of anti-N, anti-S-RBD and RBD-ACE2 blocking antibodies after the second vaccine dose compared to infection-naïve individuals (n = 48). Post-vaccination SARS-CoV-2-specific antibody responses rapidly waned in infection-naïve individuals. Antibody responses wane after vaccination, making individuals susceptible to infection by SARS-CoV-2 variants. These findings support the need for booster doses after primary vaccination. Population antibody serosurveys provide critical information toward implementing optimal timing of booster doses.

Journal article

Altmann DM, Boyton RJ, 2023, Outsourcing covid-19 vaccination to the private sector will increase health inequalities, BMJ: British Medical Journal, Vol: 382, Pages: 2012-2012, ISSN: 0959-535X

Journal article

Altmann DM, Reynolds CJ, Joy G, Otter AD, Gibbons JM, Pade C, Swadling L, Maini MK, Brooks T, Semper A, McKnight Á, Noursadeghi M, Manisty C, Treibel TA, Moon JC, Boyton RJet al., 2023, Persistent symptoms after COVID-19 are not associated with differential SARS-CoV-2 antibody or T cell immunity, Nature Communications, Vol: 14, Pages: 1-9, ISSN: 2041-1723

Among the unknowns in decoding the pathogenesis of SARS-CoV-2 persistent symptoms in Long Covid is whether there is a contributory role of abnormal immunity during acute infection. It has been proposed that Long Covid is a consequence of either an excessive or inadequate initial immune response. Here, we analyze SARS-CoV-2 humoral and cellular immunity in 86 healthcare workers with laboratory confirmed mild or asymptomatic SARS-CoV-2 infection during the first wave. Symptom questionnaires allow stratification into those with persistent symptoms and those without for comparison. During the period up to 18-weeks post-infection, we observe no difference in antibody responses to spike RBD or nucleoprotein, virus neutralization, or T cell responses. Also, there is no difference in the profile of antibody waning. Analysis at 1-year, after two vaccine doses, comparing those with persistent symptoms to those without, again shows similar SARS-CoV-2 immunity. Thus, quantitative differences in these measured parameters of SARS-CoV-2 adaptive immunity following mild or asymptomatic acute infection are unlikely to have contributed to Long Covid causality. ClinicalTrials.gov (NCT04318314).

Journal article

Jackson C, Stewart ID, Plekhanova T, Cunningham PS, Hazel AL, Al-Sheklly B, Aul R, Bolton CE, Chalder T, Chalmers JD, Chaudhuri N, Docherty AB, Donaldson G, Edwardson CL, Elneima O, Greening NJ, Hanley NA, Harris VC, Harrison EM, Ho L-P, Houchen-Wolloff L, Howard LS, Jolley CJ, Jones MG, Leavy OC, Lewis KE, Lone NI, Marks M, McAuley HJC, McNarry MA, Patel BV, Piper-Hanley K, Poinasamy K, Raman B, Richardson M, Rivera-Ortega P, Rowland-Jones SL, Rowlands AV, Saunders RM, Scott JT, Sereno M, Shah AM, Shikotra A, Singapuri A, Stanel SC, Thorpe M, Wootton DG, Yates T, Gisli Jenkins R, Singh SJ, Man WD-C, Brightling CE, Wain LV, Porter JC, Thompson AAR, Horsley A, Molyneaux PL, Evans RA, Jones SE, Rutter MK, Blaikley JF, PHOSP-COVID Study Collaborative Groupet al., 2023, Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study, The Lancet Respiratory Medicine, Vol: 11, Pages: 673-684, ISSN: 2213-2600

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended

Journal article

da Silva Duarte G, Jones AD, de Goes Cavalcanti LP, de Melo Rêgo MJB, Ribeiro GS, Boyton RJ, Pereira DB, Croda JHR, Costa FTM, Duarte AP, Consolaro MEL, Stabeli RG, Negrão FJ, Proenca-Modena JL, Villalobos-Salcedo JM, da Rocha Castelar Pinheiro G, de Barros Albuquerque AP, de Almeida Barreto FK, Moreira J, Ferrari IC, Évora PM, da Silva VRS, Lacerda MVG, Altmann DM, REPLICK network, Siqueira AMet al., 2023, Multicenter study of the natural history and therapeutic responses of patients with chikungunya, focusing on acute and chronic musculoskeletal manifestations - a study protocol from the clinical and applied research in Chikungunya (REPLICK network), BMC Infectious Diseases, Vol: 23, Pages: 1-12, ISSN: 1471-2334

BACKGROUND: Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. METHODS: The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science - comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. DISCUSSI

Journal article

Altmann DM, Whettlock EM, Liu S, Arachchillage DJ, Boyton RJet al., 2023, The immunology of long COVID, Nature Reviews Immunology, ISSN: 1474-1733

Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge. Long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, multi-organ, multisystem and relapsing-remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities. Diverse auto-antibody (AAB) specificities have been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein-Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic aetiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways.

Journal article

Boyton RJ, Altmann DM, 2023, Imprinted hybrid immunity against XBB reinfection, Lancet Infectious Diseases, Vol: 23, Pages: 764-765, ISSN: 1473-3099

Journal article

Milighetti M, Peng Y, Tan C, Mark M, Nageswaran G, Byrne S, Ronel T, Peacock T, Mayer A, Chandran A, Rosenheim J, Whelan M, Yao X, Liu G, Felce SL, Dong T, Mentzer AJ, Knight JC, Balloux F, Greenstein E, Reich-Zeliger S, Pade C, Gibbons JM, Semper A, Brooks T, Otter A, Altmann DM, Boyton RJ, Maini MK, McKnight A, Manisty C, Treibel TA, Moon JC, COVIDsortium Investigators, Noursadeghi M, Chain Bet al., 2023, Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection, iScience, Vol: 26, Pages: 1-20, ISSN: 2589-0042

T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis of this rapid response following SARS-COV-2 infection. We applied T cell receptor (TCR) sequencing to define the trajectories of individual T cell clones immediately. In SARS-COV-2 PCR+ individuals, a wave of TCRs strongly but transiently expand, frequently peaking the same week as the first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated as SARS-COV-2 specific. Epitopes recognized by the expanding TCRs were highly conserved between SARS-COV-2 strains but not with circulating human coronaviruses. Many expanding CDR3s were present at high frequency in pre-pandemic repertoires. Early response TCRs specific for lymphocytic choriomeningitis virus epitopes were also found at high frequency in the preinfection naive repertoire. High-frequency naive precursors may allow the T cell response to respond rapidly during the crucial early phases of acute viral infection.

Journal article

Zheng B, Vivaldi G, Daines L, Leavy OC, Richardson M, Elneima O, McAuley HJC, Shikotra A, Singapuri A, Sereno M, Saunders RM, Harris VC, Houchen-Wolloff L, Greening NJ, Pfeffer PE, Hurst JR, Brown JS, Shankar-Hari M, Echevarria C, De Soyza A, Harrison EM, Docherty AB, Lone N, Quint JK, Chalmers JD, Ho L-P, Horsley A, Marks M, Poinasamy K, Raman B, Heaney LG, Wain LV, Evans RA, Brightling CE, Martineau A, Sheikh A, 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, Aul R, 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, Baldwin M, 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, Beirne P, 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, Bolton CE, Bonnington J, Botkai A, Bourne C, Bourne M, Bramham K, Brear L, Breen G, Breeze J, Briggs A, Bright E, Brightling CE, Brill S, Brindle K, Broad L, Broadley A, Brookes C, Broome M, Brown A, Brown J, Brown JS, Brown M, Brown V, Brugha T, Brunskill N, Buch M, Buckley P, Bularga A, Bullmore E, Burden L, Burdett T, Burn D, Burns G, Burns A, Busby J, Butcher R, Butt A, Byrne S, Cairns P, Calder PC, Calvelo E, Carborn H, Card B, Carr C, Carr L, Carson G, Carter P, Casey A, Cassar M, Cavanagh J, Chablani M, Chalder T, Chalmers JD, Chambers RC, Chan F, Channon KM, Chapman Ket al., 2023, Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls, The Lancet Regional Health. Europe, Vol: 29, Pages: 1-13, ISSN: 2666-7762

BackgroundThe risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea.MethodsWe used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up.FindingsWe included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission).InterpretationFactors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19.FundingPHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publica

Journal article

Boyton RJ, Altmann DM, 2023, Redirected vaccine imprinting by co-administration of COVID-19 and influenza vaccines, The Lancet Regional Health. Europe, Vol: 29, ISSN: 2666-7762

Journal article

McAuley HJC, Evans RA, Bolton CE, Brightling CE, Chalmers JD, Docherty AB, Elneima O, Greenhaff PL, Gupta A, Harris VC, Harrison EM, Ho L-P, Horsley A, Houchen-Wolloff L, Jolley CJ, Leavy OC, Lone NI, Man WD-C, Marks M, Parekh D, Poinasamy K, Quint JK, Raman B, Richardson M, Saunders RM, Sereno M, Shikotra A, Singapuri A, Singh SJ, Steiner M, Tan AL, Wain LV, Welch C, Whitney J, Witham MD, Lord J, Greening NJ, PHOSP-COVID Study Collaborative Groupet al., 2023, Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study., EClinicalMedicine, Vol: 57, Pages: 1-13, ISSN: 2589-5370

BACKGROUND: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. METHODS: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group-robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)-at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. FINDINGS: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. INTERPRETATION: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although

Journal article

Altmann DM, 2023, The COVID-19 immunology masterclass enters its third year, NATURE IMMUNOLOGY, Vol: 24, Pages: 201-202, ISSN: 1529-2908

Journal article

Liu Z, Le K, Zhou X, Alexander J, Lin S, Bewshea C, Chanchlani N, Nice R, McDonald T, Lamb C, Sebastian S, Kok K, Lees C, Hart A, Pollok R, Boyton R, Altmann DM, Pollock KM, Goodhand J, Kennedy N, Ahmad T, Powell Net al., 2023, Neutralising antibody potency against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants in infliximab and vedolizumab treated patients with inflammatory bowel disease after three doses of COVID-19 vaccine: a prospective multicentre cohort study (CLARITY), The Lancet Gastroenterology & Hepatology, Vol: 8, Pages: 145-156, ISSN: 2468-1253

Background:Anti-tumour necrosis factor (TNF) drugs such as infliximab are associated with attenuated antibody responses after COVID-19 vaccination. It is unknown how infliximab impacts vaccine-induced serological responses against highly transmissible Omicron variants, which possess the ability to evade host immunity and are now the dominating variants causing current waves of infection. Methods:CLARITY IBD is a prospective, multicentre, observational cohort study investigating the impact of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). In the current work, the primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants after three doses of COVID-19 vaccination in 1288 patients with IBD without prior COVID-19 infection, who were established on either infliximab (n=871) or vedolizumab (n=417). Cox proportional hazards models were constructed to investigate the risk of breakthrough infection in relation to neutralising antibody titres.Findings:Following three doses of COVID-19 vaccine, neutralising titre NT50 (half-inhibitory neutralising titre) was significantly diminished in patients treated with infliximab as compared to patients treated with vedolizumab, against wild-type (geometric mean [95% CI], 1990 [1781, 2223] vs 3212 [2780, 3712], p<0·0001), BA.1 (95·46 [82·80, 110·0] vs 599·1 [492·6, 728·6], p<0·0001) and BA.4/5 (30·73 [26·26, 35·96] vs 212·2 [177·0, 254·4], p<0·0001) variants. Breakthrough infection was significantly more frequent in patients treated with infliximab (13·66% [11·49%, 16·16%], 119/871) compared to patients treated with vedolizumab (6·95% [4·79%, 9·95%], 29/417, p=0·0004). Cox proportional hazards models of time to breakthrough infection after the third d

Journal article

Kennedy NA, Janjua M, Chanchlani N, Lin S, Bewshea C, Nice R, McDonald TJ, Auckland C, Harries LW, Davies M, Michell S, Kok KB, Lamb CA, Smith PJ, Hart AL, Pollok RCG, Lees CW, Boyton RJ, Altmann DM, Sebastian S, Powell N, Goodhand JR, Ahmad Tet al., 2023, Vaccine escape, increased breakthrough and reinfection in infliximab-treated patients with IBD during the Omicron wave of the SARS-CoV-2 pandemic, Gut, Vol: 72, Pages: 295-305, ISSN: 0017-5749

Objective Antitumour necrosis factor (TNF) drugs impair serological responses following SARS-CoV-2 vaccination. We sought to assess if a third dose of a messenger RNA (mRNA)-based vaccine substantially boosted anti-SARS-CoV-2 antibody responses and protective immunity in infliximab-treated patients with IBD.Design Third dose vaccine induced anti-SARS-CoV-2 spike (anti-S) receptor-binding domain (RBD) antibody responses, breakthrough SARS-CoV-2 infection, reinfection and persistent oropharyngeal carriage in patients with IBD treated with infliximab were compared with a reference cohort treated with vedolizumab from the impaCt of bioLogic therApy on saRs-cov-2 Infection and immuniTY (CLARITY) IBD study.Results Geometric mean (SD) anti-S RBD antibody concentrations increased in both groups following a third dose of an mRNA-based vaccine. However, concentrations were lower in patients treated with infliximab than vedolizumab, irrespective of whether their first two primary vaccine doses were ChAdOx1 nCoV-19 (1856 U/mL (5.2) vs 10 728 U/mL (3.1), p<0.0001) or BNT162b2 vaccines (2164 U/mL (4.1) vs 15 116 U/mL (3.4), p<0.0001). However, no differences in anti-S RBD antibody concentrations were seen following third and fourth doses of an mRNA-based vaccine, irrespective of the combination of primary vaccinations received. Post-third dose, anti-S RBD antibody half-life estimates were shorter in infliximab-treated than vedolizumab-treated patients (37.0 days (95% CI 35.6 to 38.6) vs 52.0 days (95% CI 49.0 to 55.4), p<0.0001).Compared with vedolizumab-treated, infliximab-treated patients were more likely to experience SARS-CoV-2 breakthrough infection (HR 2.23 (95% CI 1.46 to 3.38), p=0.00018) and reinfection (HR 2.10 (95% CI 1.31 to 3.35), p=0.0019), but this effect was uncoupled from third vaccine dose anti-S RBD antibody concentrations. Reinfection occurred predominantly during the Omicron wave and was predicted by SARS-CoV-2 antinucleocapsid concentr

Journal article

Milojkovic D, Reynolds CJ, Sandoval DM, Pieper FP, Liu S, Pade C, Gibbons JM, McKnight A, Loaiza S, Palanicawander R, Innes AJ, Claudiani S, Apperley JF, Altmann DM, Boyton RJet al., 2023, COVID-19 vaccine boosted immunity against Omicron in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors, LEUKEMIA, Vol: 37, Pages: 244-247, ISSN: 0887-6924

Journal article

Liew F, Talwar S, Cross A, Willett B, Scott S, Logan N, Siggins M, Swieboda D, Sidhu J, Efstathiou C, Moore S, Davis C, Mohamed N, Nunag J, King C, Thompson AAR, Rowland-Jones S, Docherty A, Chalmers J, Ho L-P, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard L, Wootton D, Dunachie S, Quint J, Evans R, Wain L, Fontanella S, de Silva T, Ho A, Harrison E, Baillie JK, Semple MG, Brightling C, Thwaites R, Turtle L, Openshaw Pet al., 2023, SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination, EBioMedicine, Vol: 87, Pages: 1-14, ISSN: 2352-3964

Background:Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.Methods:In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.Findings:Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.Interpretation:The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.Funding:This

Journal article

Captur G, Moon JC, Topriceanu C-C, Joy G, Swadling L, Hallqvist J, Doykov I, Patel N, Spiewak J, Baldwin T, Hamblin M, Menacho K, Fontana M, Treibel TA, Manisty C, O'Brien B, Gibbons JM, Pade C, Brooks T, Altmann DM, Boyton RJ, McKnight Á, Maini MK, Noursadeghi M, Mills K, Heywood WE, UK COVIDsortium Investigatorset al., 2022, Plasma proteomic signature predicts who will get persistent symptoms following SARS-CoV-2 infection, EBioMedicine, Vol: 85, Pages: 1-14, ISSN: 2352-3964

BACKGROUND: The majority of those infected by ancestral Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the UK first wave (starting March 2020) did not require hospitalisation. Most had a short-lived mild or asymptomatic infection, while others had symptoms that persisted for weeks or months. We hypothesized that the plasma proteome at the time of first infection would reflect differences in the inflammatory response that linked to symptom severity and duration. METHODS: We performed a nested longitudinal case-control study and targeted analysis of the plasma proteome of 156 healthcare workers (HCW) with and without lab confirmed SARS-CoV-2 infection. Targeted proteomic multiple-reaction monitoring analysis of 91 pre-selected proteins was undertaken in uninfected healthcare workers at baseline, and in infected healthcare workers serially, from 1 week prior to 6 weeks after their first confirmed SARS-CoV-2 infection. Symptom severity and antibody responses were also tracked. Questionnaires at 6 and 12 months collected data on persistent symptoms. FINDINGS: Within this cohort (median age 39 years, interquartile range 30-47 years), 54 healthcare workers (44% male) had PCR or antibody confirmed infection, with the remaining 102 (38% male) serving as uninfected controls. Following the first confirmed SARS-CoV-2 infection, perturbation of the plasma proteome persisted for up to 6 weeks, tracking symptom severity and antibody responses. Differentially abundant proteins were mostly coordinated around lipid, atherosclerosis and cholesterol metabolism pathways, complement and coagulation cascades, autophagy, and lysosomal function. The proteomic profile at the time of seroconversion associated with persistent symptoms out to 12 months. Data are available via ProteomeXchange with identifier PXD036590. INTERPRETATION: Our findings show that non-severe SARS-CoV-2 infection perturbs the plasma proteome for at least 6 weeks. The plasma proteomic signature at th

Journal article

Alexander J, Liu Z, Munoz Sandoval D, Reynolds C, Ibraheim H, Saifuddin M, Constable L, Altmann D, Balarajah S, Hicks L, Williams H, Teare J, Hart A, Boyton R, Powell Net al., 2022, COVID-19 vaccine-induced antibody and T cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose: a multicentre, prospective, case-control study, The Lancet Gastroenterology & Hepatology, Vol: 7, Pages: 1005-1015, ISSN: 2468-1253

Background:COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to determine whether immunosuppressive treatments were associated with reduced antibody and T cell responses after a third vaccine dose.Methods:352 adults (72 healthy controls and 280 IBD) were sampled 28-49 days after a third dose of SARS-CoV-2 vaccine. IBD medications studied included thiopurines (n=65), infliximab (n=46), thiopurine/infliximab combination therapy (n=49), ustekinumab (n=44), vedolizumab (n=50) or tofacitinib (n=26). SARS-CoV-2 spike antibody binding and T cell responses were measured. Findings:Geometric mean [geometric SD] anti-S1 RBD antibody concentrations increased in all groups following a third dose, but were significantly lower in patients treated with infliximab (2736.8 U/mL [4.3]; P<0.0001), infliximab and thiopurine combination (1818.3 U/mL [6.7]; P<0.0001) and tofacitinib (8071.5 U/mL [3.1]; P=0.0018) compared to controls (16774.2 U/ml [2.6]). There were no significant differences in anti-S1 RBD antibody concentrations between control subjects and thiopurine (12019.7 U/mL [2.2]; P=0.099), ustekinumab (11089.3 U/mL [2.8]; P=0.060), nor vedolizumab treated patients (13564.9 U/mL [2.4]; P=0.27). In multivariable modelling, lower anti-S1 RBD antibody concentrations were independently associated with infliximab (Geometric mean ratio 0.15, 95% CI 0.11-0.21, P<0.0001), tofacitinib (0.52, 95% CI 0.31-0.87, P=0.012) and thiopurine (0.69, 95% CI 0.51-0.95, P=0.021), but not with ustekinumab (0.64, 95% CI 0.39-1.06, P=0.083), or vedolizumab (0.84, 95% CI 0.54-1.30, P=0.43). Previous SARS-CoV-2 infection (1.58, 95% CI 1.22-2.05, P=0.00056) and older age (0.88, 95% CI 0.80-0.97, P=0.0073) were independently associated with higher and lower anti-S1 antibody concentrations respectively. Antigen specific T cell responses were similar in all groups, except for reci

Journal article

de Morais Batista F, Puga MAM, da Silva PV, Oliveira R, Dos Santos PCP, da Silva BO, Tatara MB, Tsuha DH, Dos Santos Pires MA, Gonçalves CCM, Pessoa E Silva R, Ferreira NT, de Barros Albuquerque AP, da Silva Duarte G, Consolaro MEL, Negrão FJ, Ferrari IC, de Goes Cavalcanti LP, Trinta KS, Ribeiro GS, de Melo Rêgo MJB, Boyton RJ, Siqueira AM, Altmann DM, Croda Jet al., 2022, Serum biomarkers associated with SARS-CoV-2 severity, Scientific Reports, Vol: 12, ISSN: 2045-2322

Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity.

Journal article

Ascough S, Ingram RJ, Chu KKY, Moore SJ, Gallagher T, Dyson H, Doganay M, Metan G, Ozkul Y, Baillie L, Williamson ED, Robinson JH, Maillere B, Boyton RJ, Altmann DMet al., 2022, Impact of HLA polymorphism on the immune response to bacillus anthracis protective antigen in vaccination versus natural infection, Vaccines, Vol: 10, Pages: 1-17, ISSN: 2076-393X

The causative agent of anthrax, Bacillus anthracis, evades the host immune response and establishes infection through the production of binary exotoxins composed of Protective Antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). The majority of vaccination strategies have focused upon the antibody response to the PA subunit. We have used a panel of humanised HLA class II transgenic mouse strains to define HLA-DR-restricted and HLA-DQ-restricted CD4+ T cell responses to the immunodominant epitopes of PA. This was correlated with the binding affinities of epitopes to HLA class II molecules, as well as the responses of two human cohorts: individuals vaccinated with the Anthrax Vaccine Precipitated (AVP) vaccine (which contains PA and trace amounts of LF), and patients recovering from cutaneous anthrax infections. The infected and vaccinated cohorts expressing different HLA types were found to make CD4+ T cell responses to multiple and diverse epitopes of PA. The effects of HLA polymorphism were explored using transgenic mouse lines, which demonstrated differential susceptibility, indicating that HLA-DR1 and HLA-DQ8 alleles conferred protective immunity relative to HLA-DR15, HLA-DR4 and HLA-DQ6. The HLA transgenics enabled a reductionist approach, allowing us to better define CD4+ T cell epitopes. Appreciating the effects of HLA polymorphism on the variability of responses to natural infection and vaccination is vital in planning protective strategies against anthrax.

Journal article

Doykov I, Baldwin T, Spiewak J, Gilmour KC, Gibbons JM, Pade C, Reynolds C, McKnight Á, Noursadeghi M, Maini MK, Manisty C, Treibel T, Captur G, Fontana M, Boyton RJ, Altmann DM, Brooks T, Semper A, UK COVIDsortium Investigators, Moon JC, Mills K, Heywood WEet al., 2022, Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response, Cell Reports Methods, Vol: 2, Pages: 1-15, ISSN: 2667-2375

Determining the protection an individual has to SARS-CoV-2 variants of concern (VoC) is crucial for future immune surveillance, vaccine development and understanding the changing immune response. We devised a more informative assay to current ELISA based serology using multiplexed, baited, targeted-proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection, or first and second dose vaccination demonstrate this approach shows concordance with existing serology and neutralisation. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.1) VoC. and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r>0.82) and may better reflect neutralisation to VoC. Analysing additional immunoproteins beyond IgG, provides important information about our understanding of the response to infection and vaccination.

Journal article

Abhishek A, Boyton RJ, Peckham N, McKnight Á, Coates LC, Bluett J, Barber V, Cureton L, Francis A, Appelbe D, Eldridge L, Julier P, Valdes AM, Brooks T, Rombach I, Altmann DM, Nguyen-Van-Tam JS, Williams HC, Cook JA, VROOM study investigatorset al., 2022, Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): a randomised, open label, superiority trial, The Lancet Respiratory Medicine, Vol: 10, Pages: 840-850, ISSN: 2213-2600

BACKGROUND: Immunosuppressive treatments inhibit vaccine-induced immunity against SARS-CoV-2. We evaluated whether a 2-week interruption of methotrexate treatment immediately after the COVID-19 vaccine booster improved antibody responses against the S1 receptor-binding domain (S1-RBD) of the SARS-CoV-2 spike protein compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. METHODS: We did an open-label, prospective, two-arm, parallel-group, multicentre, randomised, controlled, superiority trial in 26 hospitals in the UK. We recruited adults from rheumatology and dermatology clinics who had been diagnosed with an immune-mediated inflammatory disease (eg, rheumatoid arthritis, psoriasis with or without arthritis, axial spondyloarthritis, atopic dermatitis, polymyalgia rheumatica, and systemic lupus erythematosus) and who were taking low-dose weekly methotrexate (≤25 mg per week) for at least 3 months. Participants also had to have received two primary vaccine doses from the UK COVID-19 vaccination programme. We randomly assigned the participants (1:1), using a centralised validated computer randomisation program, to suspend methotrexate treatment for 2 weeks immediately after their COVID-19 booster (suspend methotrexate group) or to continue treatment as usual (continue methotrexate group). Participants, investigators, clinical research staff, and data analysts were unmasked, while researchers doing the laboratory analyses were masked to group assignment. The primary outcome was S1-RBD antibody titres 4 weeks after receiving the COVID-19 booster vaccine dose, assessed in the intention-to-treat population. This trial is registered with ISRCT, ISRCTN11442263; following the pre-planned interim analysis, recruitment was stopped early. FINDINGS: Between Sept 30, 2021 and March 3, 2022, we recruited 340 participants, of whom 254 were included in the interim analysis and had been randomly assigned to one of the two groups: 127 in the co

Journal article

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