Imperial College London

DrElizabethWhittaker

Faculty of MedicineDepartment of Infectious Disease

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2063e.whittaker

 
 
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Location

 

PaediatricsNorfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

90 results found

Cohen JM, Bamford A, Eisen S, Emonts M, Ho D, Kadambari S, Kenny J, Lyall H, Owens S, Porter D, Riordan A, Whittaker E, Williams B, Ladhani S, Royal College of Paediatrics and Child Health Monkeypox Working Groupet al., 2022, Comment Title: Care of children exposed to monkeypox., Lancet Reg Health Eur, Vol: 21

Journal article

Ranasinghe L, Achar J, Groschel M, Whittaker E, Dodd P, Seddon Jet al., 2022, The global impact of COVID-19 on childhood tuberculosis: analysis of notification data, The Lancet Global Health, ISSN: 2214-109X

Background:There is concern that the Coronavirus Disease-19 (COVID-19) pandemic has damaged global childhood tuberculosis management. Quantifying changes in child tuberculosis notifications could support more targeted interventions to restore child tuberculosis services.Methods: Annual case notification data reported to the World Health Organization (WHO) by 215 countries were used to calculate annual notification counts for 2014-2020 stratified by age groups (0-4, 5-14 and 15+ years) and sex. We used time series modelling to predict notification counts for 2020, and calculated differences from observed 2020 notifications at WHO region level and country-level for the 30 high tuberculosis-burden countries. We assessed association between these differences and the Oxford Government Response Tracker, a measure of COVID-19 social impact. Findings:Before 2020, annual notification counts increased across all age groups and WHO regions. More males than females 0-4 years were notified in all years and WHO regions. In 2020, global notifications for children 0-4 years were 35.4% lower than predicted (95% prediction interval [PI] -30.3 to -39.9), compared to 27.7% lower (95% PI: -23.4 to -31.5) in children 5-14 years and 18.8% lower (95%PI; -15.4 to -21.9) in 15+ years. The difference between predicted and observed notifications for 2020 were greater in males (-30.9%; 95%PI: -24.8 to -36.1) than females (-24.5%; 95%PI: -18.1 to –29.9%). No association was seen between severity of COVID-19 restrictions and change in notifications.Interpretation:Our findings suggest that COVID-19 has substantially impacted child tuberculosis services with the youngest children most affected. Although children suffered fewer severe health consequences from COVID-19 infection, they have been disproportionately affected by the consequences of the pandemic on tuberculosis care. As countries rebuild health systems post-COVID-19, it is vital that childhood tuberculosis services are placed centr

Journal article

Harwood R, Rad L, Kelly C, Shelton C, Shepherd E, Roderick M, Whittaker E, Dyke S, Patel SV, Gent N, Kenny SEet al., 2022, Lateral flow test performance in children for SARS-CoV-2 using anterior nasal and buccal swabbing: sensitivity, specificity, negative and positive predictive values, Archives of Disease in Childhood, ISSN: 0003-9888

<jats:sec><jats:title>Objective</jats:title><jats:p>To determine if the sensitivity of the lateral flow test is dependent on the viral load and on the location of swabbing in the respiratory tract in children.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Phase 1: Routinely performed reverse transcriptase PCR (RT-PCR) using nose and throat (NT) swabs or endotracheal (ET) aspirates were compared with Innova lateral flow tests (LFTs) using anterior nasal (AN) swabs. Phase 2: RT-PCR-positive children underwent paired AN RT-PCR and LFT and/or paired AN RT-PCR and buccal LFT.</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>Tertiary paediatric hospitals.</jats:p></jats:sec><jats:sec><jats:title>Patients</jats:title><jats:p>Children under the age of 18 years. Phase 1: undergoing routine testing, phase 2: known SARS-CoV-2 positive.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Phase 1: 435 paired swabs taken in 431 asymptomatic patients resulted in 8 positive RT-PCRs, 9 PCR test failures and 418 negative RT-PCRs from NT or ET swabs. The test performance of AN LFT demonstrated sensitivity: 25% (4%–59%), specificity: 100% (99%–100%), positive predictive value (PPV): 100% (18%–100%) and negative predictive value (NPV): 99% (97%–99%).</jats:p><jats:p>Phase 2: 14 AN RT-PCR-positive results demonstrated a sensitivity of 77% (50%–92%) of LFTs performed on AN swabs. 15/16 paired buccal LFT swabs were negative.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The NPV, PPV and specificity of LFTs are excellent. The sensitivity of LFTs compared with RT-PCR is good when the samples are colocated but may be reduced when the LFT swab is taken from the AN. Buc

Journal article

Duret A, Olgemoeller F, Ferreras-Antolin L, Whittaker E, Cohen JMet al., 2022, Paediatric TB care in the United Kingdom, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 26, Pages: 814-819, ISSN: 1027-3719

Journal article

Hoste L, MIS-C researchers, Soriano-Arandes A, Buddingh EP, Whittaker E, Belot A, Ulloa-Gutierrez R, Olbrich P, Haerynck Fet al., 2022, Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Children with a History of Multisystem Inflammatory Syndrome in Children: An International Survey., J Pediatr, Vol: 248, Pages: 114-118

The optimal severe acute respiratory syndrome coronavirus 2 vaccine strategy for patients with a history of multisystem inflammatory syndrome in children (MIS-C) is unclear. We performed an international survey (32 countries) and found substantial variations in vaccine policies. Respondents did not report relapses of MIS-C or other severe inflammatory side effects after severe acute respiratory syndrome coronavirus 2 vaccination in 273 patients with a history of MIS-C.

Journal article

Cardoso Pinto A, Ranasinghe L, Dodd P, Budhathoki SS, Seddon J, Whittaker Eet al., 2022, Disruptions to routine childhood vaccinations in low- and middle-Income countries during the COVID-19 pandemic: a systematic review, Frontiers in Pediatrics, Vol: 10, ISSN: 2296-2360

BackgroundThe COVID-19 pandemic has disrupted routine childhood vaccinations worldwide with low- and middle-income countries (LMICs) most affected. This study aims to quantify levels of disruption to routine vaccinations in LMICs. MethodsA systematic review (PROSPERO CRD42021286386) was conducted of MEDLINE, Embase, Global Health, CINAHL, Scopus and MedRxiv, on the 11th of February 2022. Primary research studies published from January 2020 onwards were included if they reported levels of routine paediatric vaccinations before and after March 2020. Study appraisal was performed using NHLBI tool for cross-sectional studies. Levels of disruption were summarised using medians and interquartile ranges. ResultsA total of 39 cross-sectional studies were identified. These showed an overall relative median decline of 10.8% (interquartile range [IQR] -27.6%, -1.4%) across all vaccines. Upper-middle-income countries (upper-MICs) (-14.3%; IQR -24.3%, -2.4%) and lower-MICs (-18.0%; IQR 48.6%, 4.1%) showed greater declines than low-income countries (-3.1%; IQR -12.8%, 2.9%), as did vaccines administered at birth (-11.8%; IQR -27.7%, -3.5%) compared to those given after birth (-8.0%; IQR -28.6%, -0.4%). Declines during the first three months of the pandemic ( 8.1%; IQR -35.1%, -1.4%) were greater than during the remainder of 2020 (-3.9%; IQR 13.0%, 11.4%) compared to baseline. ConclusionThere has been a decline in routine paediatric vaccination, greatest in MICs and for vaccines administered at birth. Nations must prioritise catch-up programmes alongside public health messaging to encourage vaccine uptake.

Journal article

Piccinelli E, Bautista-Rodriguez C, Herberg J, Kang H, Krupickova S, Altamar IB, Moscatelli S, Sabatino J, Josen M, Paredes J, Whittaker E, Singh Y, Fraisse A, Di Salvo Get al., 2022, Segmental and global longitudinal strain differences between Kawasaki disease and multi-system inflammatory syndrome in children, CARDIOLOGY IN THE YOUNG, ISSN: 1047-9511

Journal article

Carr JP, MacLennan JM, Plested E, Bratcher HB, Harrison OB, Aley PK, Bray JE, Camara S, Rodrigues CMC, Davis K, Bartolf A, Baxter D, Cameron JC, Cunningham R, Faust SN, Fidler K, Gowda R, Heath PT, Hughes S, Khajuria S, Orr D, Raman M, Smith A, Turner DP, Whittaker E, Williams CJ, Zipitis CS, Pollard AJ, Oliver J, Morales-Aza B, Lekshmi A, Clark SA, Borrow R, Christensen H, Trotter C, Finn A, Maiden MCJ, Snape MD, UKMenCar4 and Be on the TEAM Study Collaboratorset al., 2022, Impact of meningococcal ACWY conjugate vaccines on pharyngeal carriage in adolescents: evidence for herd protection from the UK MenACWY programme., Clin Microbiol Infect

OBJECTIVES: Serogroup W and Y invasive meningococcal disease (IMD) increased globally from 2000 onwards. Responding to a rapid increase in serogroup W clonal complex 11 (W:cc11) IMD, the UK replaced an adolescent booster dose of meningococcal C conjugate vaccine with quadrivalent MenACWY conjugate vaccine in 2015. By 2018, vaccine coverage in the eligible school cohorts aged 14-19 years-old was 84%. We assessed the impact of the MenACWY vaccination programme on meningococcal carriage. METHODS: An observational study of culture-defined oropharyngeal meningococcal carriage prevalence before and after the start of the MenACWY vaccination programme in UK school students, aged 15-19 years, using two cross-sectional studies: 2014-15 "UKMenCar4" and 2018 "Be on the TEAM" (ISRCTN75858406). RESULTS: A total of 10625 participants pre-implementation and 13434 post-implementation were included. Carriage of genogroups C, W, and Y (combined) decreased from 2·03% to 0·71% (OR 0·34 [95% CI 0·27-0·44] p<0·001). Carriage of genogroup B meningococci did not change (1·26% vs 1·23% [95% CI 0.77-1.22] p=0·80) and genogroup C remained rare (n = 7/10625 vs 17/13488, p=0·135). The proportion of serogroup positive isolates, i.e., those expressing capsule, decreased for genogroup W by 53.8% (95% CI -5.0%-79.8%, p=0·016) and for genogroup Y by 30·1% (95% CI 8·9%-46·3%, p=0·0025). CONCLUSIONS: The UK MenACWY vaccination programme reduced carriage acquisition of genogroup and serogroup Y and W meningococci and sustained low levels of genogroup C carriage. These data support the use of quadrivalent MenACWY conjugate vaccine for indirect (herd) protection.

Journal article

Levin M, Whittaker E, 2022, Balancing risk and benefit of SARS-CoV-2 vaccines in children Comment, LANCET REGIONAL HEALTH-EUROPE, Vol: 18, ISSN: 2666-7762

Journal article

Vivancos R, Anderson C, Blomquist P, Balasegaram S, Bell A, Bishop L, Brown CS, Chow Y, Edeghere O, Florence I, Logan S, Manley P, Crowe W, McAuley A, Shankar AG, Mora-Peris B, Paranthaman K, Prochazka M, Ryan C, Simons D, Vipond R, Byers C, Watkins NA, Welfare W, Whittaker E, Dewsnap C, Wilson A, Young Y, Chand M, Riley S, Hopkins Set al., 2022, Community transmission of monkeypox in the United Kingdom, April to May 2022, EUROSURVEILLANCE, Vol: 27, ISSN: 1025-496X

Journal article

Welzel T, Schobi N, Andre MC, Bailey DGN, Blanchard-Rohner G, Buettcher M, Grazioli S, Koehler H, Perez M-H, Truck J, Vanoni F, Zimmermann P, Atkinson A, Sanchez C, Whittaker E, Faust SN, Bielicki JA, Schlapbach LJ, wissped RTet al., 2022, Multicenter Randomized Trial of Methylprednisolone vs. Intravenous Immunoglobulins to Treat the Pediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS): Protocol of the Swissped RECOVERY Trial, FRONTIERS IN PEDIATRICS, Vol: 10, ISSN: 2296-2360

Journal article

Johnson SM, Pinera C, Whittaker E, Kirkhope N, Kon OM, Satta G, Elvira Balcells M, Foster Cet al., 2022, Rare Mycobacteria and HIV in Children: Two Case Reports, CLINICAL DRUG INVESTIGATION, Vol: 42, Pages: 541-547, ISSN: 1173-2563

Journal article

Burkhardt I, Whittaker E, 2022, Use of single-dose tocilizumab for treatment of severe COVID-19 in pregnancy: implications for the timing of live infant vaccines, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 107, Pages: 516-516, ISSN: 0003-9888

Journal article

Swann O, Pollock L, Holden KA, Munro APS, Bennett A, Williams TC, Turtle L, Fairfield CJ, Drake TM, Faust SN, Sinha IP, Roland D, Whittaker E, Ladhani SN, Nguyen-Van-Tam JS, Girvan M, Donohue C, Donegan C, Spencer RG, Hardwick HE, Openshaw PJM, Baillie JK, Harrison EM, Docherty AB, Semple MGet al., 2022, Comparison of UK paediatric SARS-CoV-2 admissions across the first and second pandemic waves, PEDIATRIC RESEARCH, ISSN: 0031-3998

Journal article

Turkova A, Wills GH, Wobudeya E, Chabala C, Palmer M, Kinikar A, Hissar S, Choo L, Musoke P, Mulenga V, Mave V, Joseph B, LeBeau K, Thomason MJ, Mboizi RB, Kapasa M, van der Zalm MM, Raichur P, Bhavani PK, McIlleron H, Demers A-M, Aarnoutse R, Love-Koh J, Seddon JA, Welch SB, Graham SM, Hesseling AC, Gibb DM, Crook AMet al., 2022, Shorter treatment for non-severe tuberculosis in African and Indian children, New England Journal of Medicine, Vol: 386, Pages: 911-922, ISSN: 0028-4793

Background:Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen.Methods:We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment.Results:From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, −0.4 percentage points; 95% confidence interval, −2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberc

Journal article

Hammitt LL, Dagan R, Yuan Y, Cots MB, Bosheva M, Madhi SA, Muller WJ, Zar HJ, Brooks D, Grenham A, Hamren UW, Mankad VS, Ren P, Takas T, Abram ME, Leach A, Griffin MP, Villafana Tet al., 2022, Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 386, Pages: 837-846, ISSN: 0028-4793

Journal article

Ferreras-Antolin L, Irwin A, Atra A, Chapelle F, Drysdale SB, Emonts M, McMaster P, Paulus S, Patel S, Rompola M, Vergnano S, Whittaker E, Warris Aet al., 2022, Pediatric Antifungal Prescribing Patterns Identify Significant Opportunities to Rationalize Antifungal Use in Children, PEDIATRIC INFECTIOUS DISEASE JOURNAL, Vol: 41, Pages: E69-E74, ISSN: 0891-3668

Journal article

RECOVERY Collaborative Group, 2022, Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial, The Lancet, Vol: 399, Pages: 665-676, ISSN: 0140-6736

BACKGROUND: Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19. METHODS: RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (2

Journal article

Stephenson T, Pinto Pereira SM, Shafran R, de Stavola BL, Rojas N, McOwat K, Simmons R, Zavala M, O'Mahoney L, Chalder T, Crawley E, Ford TJ, Harnden A, Heyman I, Swann O, Whittaker E, Ladhani SN, Stephenson T, Shafran R, Buszewicz M, Chalder T, Crawley E, Dalrymple E, de Stavola BL, Ford T, Garg S, Semple M, Hargreaves D, Harnden A, Heyman I, Ladhani S, Levin M, Poustie V, Segal T, Sharma K, Swann O, Whittaker Eet al., 2022, Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study, The Lancet Child & Adolescent Health, Vol: 6, Pages: 230-239, ISSN: 2352-4642

BackgroundWe describe post-COVID symptomatology in a non-hospitalised, national sample of adolescents aged 11–17 years with PCR-confirmed SARS-CoV-2 infection compared with matched adolescents with negative PCR status.MethodsIn this national cohort study, adolescents aged 11–17 years from the Public Health England database who tested positive for SARS-CoV-2 between January and March, 2021, were matched by month of test, age, sex, and geographical region to adolescents who tested negative. 3 months after testing, a subsample of adolescents were contacted to complete a detailed questionnaire, which collected data on demographics and their physical and mental health at the time of PCR testing (retrospectively) and at the time of completing the questionnaire (prospectively). We compared symptoms between the test-postive and test-negative groups, and used latent class analysis to assess whether and how physical symptoms at baseline and at 3 months clustered among participants. This study is registered with the ISRCTN registry (ISRCTN 34804192).Findings23 048 adolescents who tested positive and 27 798 adolescents who tested negative between Jan 1, 2021, and March 31, 2021, were contacted, and 6804 adolescents (3065 who tested positive and 3739 who tested negative) completed the questionnaire (response rate 13·4%). At PCR testing, 1084 (35·4%) who tested positive and 309 (8·3%) who tested negative were symptomatic and 936 (30·5%) from the test-positive group and 231 (6·2%) from the test-negative group had three or more symptoms. 3 months after testing, 2038 (66·5%) who tested positive and 1993 (53·3%) who tested negative had any symptoms, and 928 (30·3%) from the test-positive group and 603 (16·2%) from the test-negative group had three or more symptoms. At 3 months after testing, the most common symptoms among the test-positive group were tiredness (1196 [39·0%]), headache (710

Journal article

Taylor A, Whittaker E, 2022, The changing epidemiology of respiratory viruses in children during the COVID-19 pandemic: A canary in a COVID time, The Pediatric Infectious Disease Journal, Vol: 41, Pages: E46-E48, ISSN: 0891-3668

Journal article

Osmanov IM, Spiridonova E, Bobkova P, Gamirova A, Shikhaleva A, Andreeva M, Blyuss O, El-Taravi Y, DunnGalvin A, Comberiati P, Peroni DG, Apfelbacher C, Genuneit J, Mazankova L, Miroshina A, Chistyakova E, Samitova E, Borzakova S, Bondarenko E, Korsunskiy AA, Konova I, Hanson SW, Carson G, Sigfrid L, Scott JT, Greenhawt M, Whittaker EA, Garralda E, Swann O, Buonsenso D, Nicholls DE, Simpson F, Jones C, Semple MG, Warner JO, Vos T, Olliaro P, Munblit D, Sechenov StopCOVID Research Teamet al., 2022, Risk factors for long covid in previoulsy hospitalsied children using the ISARIC Global Follow-Up Protocol: a prospective cohort study, European Respiratory Journal, Vol: 59, ISSN: 0903-1936

Background The long-term sequelae of coronavirus disease 2019 (Covid-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with Covid-19 and associated risk factors.Methods This is a prospective cohort study of children (≤18 years old) admitted with confirmed Covid-19. Children admitted to the hospital between April 2, 2020 and August 26, 2020, were included. Telephone interview using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Covid-19 Health and Wellbeing paediatric follow-up survey. Persistent symptoms (>5 months) were further categorised by system(s) involved.Findings 518 of 853 (61%) of eligible children were available for the follow-up assessment and included in the study. Median age was 10.4 years (IQR, 3–15.2) and 270 (52.1%) were girls; median follow-up since hospital discharge was 256 (223–271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%,) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: older age “6–11 years” (odds ratio 2.74 (95% confidence interval 1.37 to 5.75) and “12–18 years” (2.68, 1.41 to 5.4); and a history of allergic diseases (1.67, 1.04 to 2.67).Interpretation A quarter of children experienced persistent symptoms months after hospitalization with acute covid-19 infection, with almost one in ten experiencing multi-system involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up.

Journal article

Harwood R, Yan H, Talawila Da Camara N, Smith C, Ward J, Tudur-Smith C, Linney M, Clark M, Whittaker E, Saatci D, Davis PJ, Luyt K, Draper ES, Kenny SE, Fraser LK, Viner RMet al., 2022, Which children and young people are at higher risk of severe disease and death after hospitalisation with SARS-CoV-2 infection in children and young people: A systematic review and individual patient meta-analysis, EClinicalMedicine, Vol: 44, ISSN: 2589-5370

Background: We aimed to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in hospitalised children and young people (CYP), within a systematic review and individual patient meta-analysis. Methods: We searched Pubmed, European PMC, Medline and Embase for case series and cohort studies published between 1st January 2020 and 21st May 2021 which included all CYP admitted to hospital with ≥ 30 CYP with SARS-CoV-2 or ≥ 5 CYP with PIMS-TS or MIS-C. Eligible studies contained (1) details of age, sex, ethnicity or co-morbidities, and (2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted groupings of co-morbidities were eligible for narrative review. We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI).PROSPERO: CRD42021235338. Findings: 83 studies were included, 57 (21,549 patients) in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1-4 years (reference group), infants (aged <1 year) had increased odds of admission to critical care (OR 1.63 (95% CI 1.40-1.90)) and death (OR 2.08 (1.57-2.86)). Odds of death were increased amongst CYP over 10 years (10-14 years OR 2.15 (1.54-2.98); >14 years OR 2.15 (1.61-2.88)).The number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a step-wise fashion. Compared with CYP without comorbidity, odds ratios for critical care admission were: 1.49 (1.45-1.53)

Journal article

Patel H, McArdle A, Seaby E, Levin M, Whittaker Eet al., 2022, The immunopathogenesis of SARS-CoV-2 infection in children: diagnostics, treatment and prevention, CLINICAL & TRANSLATIONAL IMMUNOLOGY, Vol: 11

Journal article

Ward JL, Harwood R, Smith C, Kenny S, Clark M, Davis P, Draper E, Hargreaves D, Ladhani S, Linney M, Luyt K, Turner S, Whittaker E, Fraser LK, Viner RMet al., 2021, Risk factors for PICU admission and death among children and young people hospitalized with COVID-19 and PIMS-TS in England during the first pandemic year, NATURE MEDICINE, Vol: 28, Pages: 193-+, ISSN: 1078-8956

Journal article

Olbrich L, Stockdale L, Basu Roy R, Song R, Cicin-Sain L, Whittaker E, Prendergast AJ, Fletcher H, Seddon JAet al., 2021, Understanding the interaction between cytomegalovirus and tuberculosis in children: The way forward, PLoS Pathogens, Vol: 17, Pages: 1-21, ISSN: 1553-7366

Over 1 million children develop tuberculosis (TB) each year, with a quarter dying. Multiple factors impact the risk of a child being exposed to Mycobacterium tuberculosis (Mtb), the risk of progressing to TB disease, and the risk of dying. However, an emerging body of evidence suggests that coinfection with cytomegalovirus (CMV), a ubiquitous herpes virus, impacts the host response to Mtb, potentially influencing the probability of disease progression, type of TB disease, performance of TB diagnostics, and disease outcome. It is also likely that infection with Mtb impacts CMV pathogenesis. Our current understanding of the burden of these 2 diseases in children, their immunological interactions, and the clinical consequence of coinfection is incomplete. It is also unclear how potential interventions might affect disease progression and outcome for TB or CMV. This article reviews the epidemiological, clinical, and immunological literature on CMV and TB in children and explores how the 2 pathogens interact, while also considering the impact of HIV on this relationship. It outlines areas of research uncertainty and makes practical suggestions as to potential studies that might address these gaps. Current research is hampered by inconsistent definitions, study designs, and laboratory practices, and more consistency and collaboration between researchers would lead to greater clarity. The ambitious targets outlined in the World Health Organization End TB Strategy will only be met through a better understanding of all aspects of child TB, including the substantial impact of coinfections.

Journal article

Only GA, 2021, Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial, LANCET RESPIRATORY MEDICINE, Vol: 9, Pages: 1419-1426, ISSN: 2213-2600

Journal article

Smith C, Odd D, Harwood R, Ward J, Linney M, Clark M, Hargreaves D, Ladhani SN, Draper E, Davis PJ, Kenny SE, Whittaker E, Luyt K, Viner R, Fraser LKet al., 2021, Deaths in children and young people in England after SARS-CoV-2 infection during the first pandemic year, Nature Medicine, Vol: 28, Pages: 185-192, ISSN: 1078-8956

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rarely fatal in children and young people (CYP, <18 years old), but quantifying the risk of death is challenging because CYP are often infected with SARS-CoV-2 exhibiting no or minimal symptoms. To distinguish between CYP who died as a result of SARS-CoV-2 infection and those who died of another cause but were coincidentally infected with the virus, we undertook a clinical review of all CYP deaths with a positive SARS-CoV-2 test from March 2020 to February 2021. The predominant SARS-CoV-2 variants were wild-type and Alpha. Here we show that, of 12,023,568 CYP living in England, 3,105 died, including 61 who were positive for SARS-CoV-2. Of these deaths, 25 were due to SARS-CoV-2 infection (mortality rate, two per million), including 22 due to coronavirus disease 2019—the clinical disease associated with SARS-CoV-2 infection—and 3 were due to pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. In total, 99.995% of CYP with a positive SARS-CoV-2 test survived. CYP older than 10 years, Asian and Black ethnic backgrounds and comorbidities were over-represented in SARS-CoV-2-related deaths compared with other CYP deaths. These results are important for guiding decisions on shielding and vaccinating children. New variants might have different mortality risks and should be evaluated in a similar way.

Journal article

Speirs L, Whittaker E, 2021, Fifteen-minute consultation: What do I do with a baby born to a mother with tuberculosis?, ARCHIVES OF DISEASE IN CHILDHOOD-EDUCATION AND PRACTICE EDITION, Vol: 106, Pages: 210-215, ISSN: 1743-0585

Journal article

Stephenson T, Shafran R, De Stavola B, Rojas N, Aiano F, Amin-Chowdhury Z, McOwat K, Simmons R, Zavala M, Consortium C, Ladhani SNet al., 2021, Long COVID and the mental and physical health of children and young people: national matched cohort study protocol (the CLoCk study), BMJ Open, Vol: 11, Pages: 1-5, ISSN: 2044-6055

Introduction There is uncertainty surrounding the diagnosis, prevalence, phenotype, duration and treatment of Long COVID. This study aims to (A) describe the clinical phenotype of post-COVID symptomatology in children and young people (CYP) with laboratory-confirmed SARS-CoV-2 infection compared with test-negative controls, (B) produce an operational definition of Long COVID in CYP, and (C) establish its prevalence in CYP.Methods and analysis A cohort study of SARS-CoV-2-positive CYP aged 11–17 years compared with age, sex and geographically matched SARS-CoV-2 test-negative CYP. CYP aged 11–17 testing positive and negative for SARS-CoV-2 infection will be identified and contacted 3, 6, 12 and 24 months after the test date. Consenting CYP will complete an online questionnaire. We initially planned to recruit 3000 test positives and 3000 test negatives but have since extended our target. Data visualisation techniques will be used to examine trajectories over time for symptoms and variables measured repeatedly, separately by original test status. Summary measures of fatigue and mental health dimensions will be generated using dimension reduction methods such as latent variables/latent class/principal component analysis methods. Cross-tabulation of collected and derived variables against test status and discriminant analysis will help operationalise preliminary definitions of Long COVID.Ethics and dissemination Research Ethics Committee approval granted. Data will be stored in secure Public Health England servers or University College London’s Data Safe Haven. Risks of harm will be minimised by providing information on where to seek support. Results will be published on a preprint server followed by journal publication, with reuse of articles under a CC BY licence. Data will be published with protection against identification when there are small frequencies involved.Trial registration number ISRCTN34804192; Pre-results.

Journal article

McArdle AJ, Vito O, Patel H, Seaby EG, Shah P, Wilson C, Broderick C, Nijman R, Tremoulet AH, Munblit D, Ulloa-Gutierrez R, Carter MJ, De T, Hoggart C, Whittaker E, Herberg JA, Kaforou M, Cunnington AJ, Levin Met al., 2021, Treatment of multisystem inflammatory syndrome in children, New England Journal of Medicine, Vol: 385, Pages: 11-22, ISSN: 0028-4793

BACKGROUNDEvidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.METHODSWe performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.RESULTSData were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.CONCLUSIONSWe found n

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