Publications
126 results found
Sanchez Clemente N, Coles C, Paixao ES, et al., 2024, Paediatric, maternal, and congenital mpox: a systematic review and meta-analysis., Lancet Glob Health, Vol: 12, Pages: e572-e588
BACKGROUND: Although mpox has been detected in paediatric populations in central and west Africa for decades, evidence synthesis on paediatric, maternal, and congenital mpox, and the use of vaccines and therapeutics in these groups, is lacking. A systematic review is therefore indicated to set the research agenda. METHODS: We conducted a systematic review and meta-analysis, searching articles in Embase, Global Health, MEDLINE, CINAHL, Web of Science, Scopus, SciELO, and WHO databases from inception to April 17, 2023. We included studies reporting primary data on at least one case of confirmed, suspected, or probable paediatric, maternal, or congenital mpox in humans or the use of third-generation smallpox or mpox vaccines, targeted antivirals, or immune therapies in at least one case in our population of interest. We included clinical trials and observational studies in humans and excluded reviews, commentaries, and grey literature. A pooled estimate of the paediatric case fatality ratio was obtained using random-effects meta-analysis. This study is registered with PROSPERO (CRD420223336648). FINDINGS: Of the 61 studies, 53 reported paediatric outcomes (n=2123 cases), seven reported maternal or congenital outcomes (n=32 cases), two reported vaccine safety (n=28 recipients), and three reported transmission during breastfeeding (n=4 cases). While a subset of seven observational studies (21 children and 12 pregnant individuals) reported uneventful treatment with tecovirimat, there were no randomised trials reporting safety or efficacy for any therapeutic agent. Among children, the commonest clinical features included rash (86 [100%] of 86), fever (63 [73%] of 86), and lymphadenopathy (40 [47%] of 86). Among pregnant individuals, rash was reported in 23 (100%) of 23; fever and lymphadenopathy were less common (six [26%] and three [13%] of 23, respectively). Most paediatric complications (12 [60%] of 20) arose from secondary bacterial infections. The pooled paediatric ca
Meinhardt A, Reilly L, Kaliakatsos M, et al., 2024, Novel antivirals for severe enterovirus infection in immunocompromised hosts; A case series., J Infect, Vol: 88
RECOVERY Collaborative Group, 2024, Immunomodulatory therapy in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS, MIS-C; RECOVERY): a randomised, controlled, open-label, platform trial, The Lancet Child & Adolescent Health, Vol: 8, Pages: 190-200, ISSN: 2352-4642
BACKGROUND: Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS), also known as multisystem inflammatory syndrome in children (MIS-C) emerged in April, 2020. The paediatric comparisons within the RECOVERY trial aimed to assess the effect of intravenous immunoglobulin or corticosteroids compared with usual care on duration of hospital stay for children with PIMS-TS and to compare tocilizumab (anti-IL-6 receptor monoclonal antibody) or anakinra (anti-IL-1 receptor antagonist) with usual care for those with inflammation refractory to initial treatment. METHODS: We did this randomised, controlled, open-label, platform trial in 51 hospitals in the UK. Eligible patients were younger than 18 years and had been admitted to hospital for PIMS-TS. In the first randomisation, patients were randomly assigned (1:1:1) to usual care (no additional treatments), usual care plus methylprednisolone (10mg/kg per day for 3 consecutive days), or usual care plus intravenous immunoglobulin (a single dose of 2 g/kg). If further anti-inflammatory treatment was considered necessary, children aged at least 1 year could be considered for a second randomisation, in which patients were randomly assigned (1:2:2) to usual care, intravenous tocilizumab (12 mg/kg in patients <30 kg; 8mg/kg in patients ≥30 kg, up to a maximum dose of 800 mg), or subcutaneous anakinra (2 mg/kg once per day in patients ≥10 kg). Randomisation was by use of a web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was duration of hospital stay. Analysis was by intention to treat. For treatments assessed in each randomisation, a single Bayesian framework assuming uninformative priors for treatment was used to jointly assess the efficacy of each intervention compared with usual care. The trial was registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between May 18, 2020, and Jan 20, 2022, 237 children with PIM
Nugawela MD, Pinto Pereira SM, Rojas NK, et al., 2024, Data Resource Profile: the Children and Young People with Long COVID (CLoCk) Study., Int J Epidemiol, Vol: 53
Johnston R, Sonnappa S, Goddings A-L, et al., 2024, A review of post COVID syndrome pathophysiology, clinical presentation and management in children and young people., Paediatr Respir Rev
Post Covid Syndrome (PCS) is a complex multi-system disorder with a spectrum of presentations. Severity ranges from mild to very severe with variable duration of illness and recovery. This paper discusses the difficulties defining and describing PCS. We review the current understanding of PCS, epidemiology, and predisposing factors. We consider potential mechanisms including viral persistence, clotting dysfunction and immunity. We review presentation and diagnosis and finally consider management strategies including addressing symptom burden, rehabilitation, and novel therapies.
Skirrow H, Foley K, Bedford H, et al., 2024, Impact of pregnancy vaccine uptake and socio-demographic determinants on subsequent childhood Measles, Mumps and Rubella vaccine uptake: a UK birth cohort study, Vaccine, Vol: 42, Pages: 322-331, ISSN: 0264-410X
BACKGROUND: We examined the association between socio-demographic determinants and uptake of childhood Measles, Mumps & Rubella (MMR) vaccines and the association between pregnant women's pertussis vaccine uptake and their children's MMR vaccine uptake. METHODS: We used nationally-representative linked mother-baby electronic records from the United Kingdom's Clinical-Practice-Research-Datalink. We created a birth cohort of children born between 01.01.2000 and 12.12.2020. We estimated the proportion vaccinated with first MMR vaccine by age 2 years and first and second MMR vaccines by age 5 years. We used survival-analysis and Cox proportional hazard models to examine the association between deprivation, ethnicity and maternal age and pertussis vaccination in pregnancy and children's MMR uptake. RESULTS: Overall, 89.4 % (710,797/795,497) of children had first MMR by age 2 years and 92.6 % (736,495/795,497) by age 5 years. Among children still in the cohort when second MMR was due, 85.9 % (478,480/557,050) had two MMRs by age 5 years. Children from the most-deprived areas, children of Black ethnicity and children of mothers aged < 20 years had increased risk of being unvaccinated compared with children from the least-deprived areas, White children and children of mothers aged 31-40 years: first MMR by 5 years, adjusted Hazard Ratios (HR):0.86 (CI:0.85-0.87), HR:0.87 (CI:0.85-0.88) & HR:0.89 (CI:0.88-0.90) respectively. Deprivation was the determinant associated with the greatest risk of missed second MMR: adjusted HR:0.82 (CI:0.81-0.83). Children of mothers vaccinated in pregnancy were more likely than children of unvaccinated mothers to have MMR vaccines after adjusting for ethnicity, deprivation, and maternal age (First and Second MMRs adjusted HRs:1.43 (CI:1.41-1.45), 1.49 (CI:1.45-1.53). CONCLUSION: Children from most-deprived areas are less likely to have MMR vaccines compared with childre
Drysdale SB, Cathie K, Flamein F, et al., 2023, Nirsevimab for Prevention of Hospitalizations Due to RSV in Infants., N Engl J Med, Vol: 389, Pages: 2425-2435
BACKGROUND: The safety of the monoclonal antibody nirsevimab and the effect of nirsevimab on hospitalizations for respiratory syncytial virus (RSV)-associated lower respiratory tract infection when administered in healthy infants are unclear. METHODS: In a pragmatic trial, we randomly assigned, in a 1:1 ratio, infants who were 12 months of age or younger, had been born at a gestational age of at least 29 weeks, and were entering their first RSV season in France, Germany, or the United Kingdom to receive either a single intramuscular injection of nirsevimab or standard care (no intervention) before or during the RSV season. The primary end point was hospitalization for RSV-associated lower respiratory tract infection, defined as hospital admission and an RSV-positive test result. A key secondary end point was very severe RSV-associated lower respiratory tract infection, defined as hospitalization for RSV-associated lower respiratory tract infection with an oxygen saturation of less than 90% and the need for supplemental oxygen. RESULTS: A total of 8058 infants were randomly assigned to receive nirsevimab (4037 infants) or standard care (4021 infants). Eleven infants (0.3%) in the nirsevimab group and 60 (1.5%) in the standard-care group were hospitalized for RSV-associated lower respiratory tract infection, which corresponded to a nirsevimab efficacy of 83.2% (95% confidence interval [CI], 67.8 to 92.0; P<0.001). Very severe RSV-associated lower respiratory tract infection occurred in 5 infants (0.1%) in the nirsevimab group and in 19 (0.5%) in the standard-care group, which represented a nirsevimab efficacy of 75.7% (95% CI, 32.8 to 92.9; P = 0.004). The efficacy of nirsevimab against hospitalization for RSV-associated lower respiratory tract infection was 89.6% (adjusted 95% CI, 58.8 to 98.7; multiplicity-adjusted P<0.001) in France, 74.2% (adjusted 95% CI, 27.9 to 92.5; multiplicity-adjusted P = 0.006) in Germany, and 83.4% (adjus
Whittaker EA, 2023, Commentary: Post-COVID Condition in Children and Young People: Where Are We Now?, Pediatr Infect Dis J, Vol: 42, Pages: 1100-1101
Newlands F, Goddings A-L, Juste M, et al., 2023, Children and Young People with Long COVID-Comparing Those Seen in Post-COVID Services with a Non-Hospitalised National Cohort: A Descriptive Study., Children (Basel), Vol: 10, ISSN: 2227-9067
BACKGROUND: Post-COVID services have been set up in England to treat children with ongoing symptoms of Long COVID. To date, the characteristics of children seeking treatment from these services has not been described. PURPOSE: (1) to describe the characteristics of children aged 11-17 referred to the Pan-London Post-COVID service and (2) to compare characteristics of these children with those taking part in the United Kingdom's largest research study of Long COVID in children (CLoCk). DESIGN: Data from 95 children seeking treatment from the Post-COVID service between May 2021 and August 2022 were included in the study. Their demographic characteristics, symptom burden and the impact of infection are described and compared to children from CLoCk. RESULTS: A high proportion of children from the Post-COVID service and CLoCk reported experiencing health problems prior to the pandemic. Almost all Post-COVID service children met the research Delphi definition of Long COVID (94.6%), having multiple symptoms that impacted their lives. Symptoms were notably more severe than the participants in CLoCk. CONCLUSIONS: This study describes the characteristics of children seeking treatment for Long COVID compared to those identified in the largest longitudinal observational study to date. Post-COVID service children have more symptoms and are more severely affected by their symptoms following infection with COVID-19 than children in the CLoCk study. Research to understand predisposing factors for severity and prognostic indicators is essential to prevent this debilitating condition. Evaluation of short- and long-term outcomes of interventions by clinical services can help direct future therapy for this group.
Skirrow H, Foley K, Bedford H, et al., 2023, Maternal predictors of timeliness & uptake of Measles, Mumps & Rubella vaccine: A birth cohort study, 16th European Public Health Conference 2023, Publisher: Oxford University Press, ISSN: 1101-1262
Skirrow H, Foley K, Lewis C, et al., 2023, ‘Why did nobody ask us?’, parents’ views on childhood vaccines: A co-production research study, European Public Health Conference
Healy J, Longbottom K, Kent A, et al., 2023, On the lookout for post-streptococcal complications in the UK, ARCHIVES OF DISEASE IN CHILDHOOD, ISSN: 0003-9888
Cooray S, Price-Kuehne F, Hong Y, et al., 2023, Neuroinflammation, autoinflammation, splenomegaly and anemia caused by bi-allelic mutations in <i>IRAK4</i>, FRONTIERS IN IMMUNOLOGY, Vol: 14, ISSN: 1664-3224
Patel H, Burgner D, Whittaker E, 2023, Multisystem inflammatory syndrome in children: a longitudinal perspective on risk factors and future directions, PEDIATRIC RESEARCH, ISSN: 0031-3998
Ladhani SN, Dowell AC, Jones S, et al., 2023, Early evaluation of the safety, reactogenicity, and immune response after a single dose of modified vaccinia Ankara- Bavaria Nordic vaccine against mpox in children: a national outbreak response, LANCET INFECTIOUS DISEASES, Vol: 23, Pages: 1042-1050, ISSN: 1473-3099
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Nesr G, Whittaker E, Bain BJ, 2023, Atypical lymphocytes - from chickenpox to monkey pox, American Journal of Hematology, Vol: 98, Pages: 1333-1334, ISSN: 0361-8609
Pinto Pereira SM, Mensah A, Nugawela MD, et al., 2023, Long COVID in children and young after infection or reinfection with the Omicron variant: a prospective observational study, Journal of Pediatrics, Vol: 259, Pages: 113463-113463, ISSN: 0022-3476
To describe the prevalence of long COVID in children infected for the first time (n = 332) or reinfected (n = 243) with Omicron compared with test-negative children (n = 311). Overall, 12%-16% of those infected with Omicron met the research definition of long COVID at 3 and 6 months after infection, with no evidence of difference between cases of first positive and reinfected (Pχ2 = 0.17).
Jones CE, Bailey H, Bamford A, et al., 2023, Managing challenges in congenital CMV: current thinking, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 108, Pages: 601-607, ISSN: 0003-9888
Ward JL, Harwood R, Kenny S, et al., 2023, Pediatric Hospitalizations and ICU Admissions Due to COVID-19 and Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 in England, JAMA PEDIATRICS, ISSN: 2168-6203
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van der Velden FJS, Lim E, Gills L, et al., 2023, Biobanking and consenting to research: a qualitative thematic analysis of young people's perspectives in the North East of England, BMC Medical Ethics, Vol: 24, Pages: 1-11, ISSN: 1472-6939
BACKGROUND: Biobanking biospecimens and consent are common practice in paediatric research. We need to explore children and young people's (CYP) knowledge and perspectives around the use of and consent to biobanking. This will ensure meaningful informed consent can be obtained and improve current consent procedures. METHODS: We designed a survey, in co-production with CYP, collecting demographic data, views on biobanking, and consent using three scenarios: 1) prospective consent, 2) deferred consent, and 3) reconsent and assent at age of capacity. The survey was disseminated via the Young Person's Advisory Group North England (YPAGne) and participating CYP's secondary schools. Data were analysed using a qualitative thematic approach by three independent reviewers (including CYP) to identify common themes. Data triangulation occurred independently by a fourth reviewer. RESULTS: One hundred two CYP completed the survey. Most were between 16-18 years (63.7%, N = 65) and female (66.7%, N = 68). 72.3% had no prior knowledge of biobanking (N = 73). Acceptability of prospective consent for biobanking was high (91.2%, N = 93) with common themes: 'altruism', 'potential benefits outweigh individual risk', 'frugality', and '(in)convenience'. Deferred consent was also deemed acceptable in the large majority (84.3%, N = 86), with common themes: 'altruism', 'body integrity' and 'sample frugality'. 76.5% preferred to reconsent when cognitively mature enough to give assent (N = 78), even if parental consent was previously in place. 79.2% wanted to be informed if their biobanked biospecimen is reused (N = 80). CONCLUSION: Prospective and deferred consent acceptability for biobanking is high among CYP in the UK. Altruism, frugality, body integrity, and privacy are the most important themes. Clear communication and justification are paramount to obtain consent. Any CYP with capacity
Piccinelli E, Bautista-Rodriguez C, Herberg J, et al., 2023, Segmental and global longitudinal strain differences between Kawasaki disease and multi-system inflammatory syndrome in children, CARDIOLOGY IN THE YOUNG, Vol: 33, Pages: 1177-1183, ISSN: 1047-9511
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Swanepoel J, van der Zalm MM, Preiser W, et al., 2023, SARS-CoV-2 infection and pulmonary tuberculosis in children and adolescents: a case-control study, BMC Infectious Diseases, Vol: 23, Pages: 1-10, ISSN: 1471-2334
BackgroundThe Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic has had an impact on the global tuberculosis (TB) epidemic but evidence on the possible interaction between SARS-CoV-2 and TB, especially in children and adolescents, remains limited. We aimed to evaluate the relationship between previous infection with SARS-CoV-2 and the risk of TB in children and adolescents.MethodsAn unmatched case-control study was conducted using SARS-CoV-2 unvaccinated children and adolescents recruited into two observational TB studies (Teen TB and Umoya), between November 2020 and November 2021, in Cape Town, South Africa. Sixty-four individuals with pulmonary TB (aged < 20 years) and 99 individuals without pulmonary TB (aged < 20 years) were included. Demographics and clinical data were obtained. Serum samples collected at enrolment underwent quantitative SARS-CoV-2 anti-spike immunoglobulin G (IgG) testing using the Abbott SARS-CoV-2 IgG II Quant assay. Odds ratios (ORs) for TB were estimated using unconditional logistic regression.ResultsThere was no statistically significant difference in the odds of having pulmonary TB between those who were SARS-CoV-2 IgG seropositive and those who were seronegative (adjusted OR 0.51; 95% CI: 0.23–1.11; n = 163; p = 0.09). Of those with positive SARS-CoV-2 serology indicating prior infection, baseline IgG titres were higher in individuals with TB compared to those without TB (p = 0.04) and individuals with IgG titres in the highest tertile were more likely to have pulmonary TB compared to those with IgG levels in the lowest tertile (OR: 4.00; 95%CI: 1.13– 14.21; p = 0.03).ConclusionsOur study did not find convincing evidence that SARS-CoV-2 seropositivity was associated with subsequent pulmonary TB disease; however, the association between magnitude of SARS-CoV-2 IgG response and pulmonary TB warrants further investigat
Morfopoulou S, Buddle S, Torres Montaguth OE, et al., 2023, Genomic investigations of unexplained acute hepatitis in children, Nature, Vol: 617, Pages: 564-573, ISSN: 0028-0836
Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.
Makariou I, Richardson C, Segal T, et al., 2023, Pulmonary Function and Cardiopulmonary Exercise Testing in Children and Young People With Post-COVID Persistent Dyspnoea, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Ho A, Orton R, Tayler R, et al., 2023, Adeno-associated virus 2 infection in children with non-A-E hepatitis., Nature, Vol: 617, Pages: 555-563
An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.
Wacks M, Wortley E, Gregorowski A, et al., 2023, Fifteen-minute consultation: Managing post-COVID-19 syndrome (long COVID) in children and young people, ARCHIVES OF DISEASE IN CHILDHOOD-EDUCATION AND PRACTICE EDITION, ISSN: 1743-0585
Channon-Wells S, Vito O, McArdle AJ, et al., 2023, Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study, The Lancet Rheumatology, Vol: 5, Pages: e184-e199, ISSN: 2665-9913
BackgroundMultisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments.MethodsThe Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370.FindingsWe enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologica
Riordan A, Faust SN, Whittaker E, 2023, Where now for infection services in the NHS? What about children?, CLINICAL MEDICINE, Vol: 23, Pages: 190-191, ISSN: 1470-2118
Harwood R, Rad L, Kelly C, et al., 2023, 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, Vol: 108, Pages: 137-140, ISSN: 0003-9888
Cardoso Pinto A, Shariq S, Ranasinghe L, et al., 2023, Reasons for reductions in routine childhood immunisation uptake during the COVID-19 pandemic in low- and middle-income countries: a systematic review, PLOS Global Public Health, Vol: 3, Pages: 1-17, ISSN: 2767-3375
The coronavirus disease 2019 (COVID-19) pandemic has resulted in a substantial decline in routine immunisation coverage in children globally, especially in low- and middle-income countries (LMICs). This study summarises the reasons for disruptions to routine child immunisations in LMICs. A systematic review (PROSPERO CRD42021286386) was conducted following PRISMA 2020 guidelines. Six databases were searched: MEDLINE, Embase, Global Health, CINAHL, Scopus and MedRxiv, on 11/02/2022. Observational and qualitative studies published from January 2020 onwards were included if exploring reasons for missed immunisations during the COVID-19 pandemic in LMICs. Study appraisal used National Heart, Lung, and Blood Institute and Critical Appraisal Skills Programme tools. Reasons for disruption were defined with descriptive codes; cross-sectional (quantitative) data were summarised as mean percentages of responses weighted by study population, and qualitative data were summarised narratively. A total of thirteen studies were included describing reasons behind disruptions; 7 cross-sectional (quantitative), 5 qualitative and 1 mixed methods. Seventeen reasons for disruptions were identified. In quantitative studies (total respondents = 2,853), the most common reasons identified were fear of COVID-19 and consequential avoidance of health centres (41.2%, SD ±13.3%), followed by transport challenges preventing both families and healthcare professionals from reaching vaccination services (11.1% SD ±16.6%). Most reasons stemmed from reduced healthcare-seeking (83.4%), as opposed to healthcare-delivery issues (15.2%). Qualitative studies showed a more even balance of healthcare-seeking (49.5%) and healthcare-delivery issues (50.5%), with fear of COVID-19 remaining a major identified issue (total respondents = 92). The most common reasons for disruption were parental fear of COVID-19 and avoidance of health services. Health systems must therefore prioritise public health me
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