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2.
J Infect ; 87(1): 18-26, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37085049

RESUMEN

BACKGROUND: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave. This report compares the immunogenicity and kinetics of responses to third doses of vaccines from day (D) 28 to D242 following third doses in seven study arms. METHODS: The trial initially included ten experimental vaccine arms (seven full-dose, three half-dose) delivered at three groups of six sites. Participants in each site group were randomised to three or four experimental vaccines, or MenACWY control. The trial was stratified such that half of participants had previously received two primary doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) and half had received two doses of BNT162b2 (Pfizer-BioNtech, hereafter referred to as BNT). The D242 follow-up was done in seven arms (five full-dose, two half-dose). The BNT vaccine was used as the reference as it was the most commonly deployed third-dose vaccine in clinical practice in high-income countries. The primary analysis was conducted using all randomised and baseline seronegative participants who were SARS-CoV-2 naïve during the study and who had not received a further COVID-19 vaccine for any reason since third dose randomisation. RESULTS: Among the 817 participants included in this report, the median age was 72 years (IQR: 55-78) with 50.7% being female. The decay rates of anti-spike IgG between vaccines are different among both populations who received initial doses of ChAd/ChAd and BNT/BNT. In the population that previously received ChAd/ChAd, mRNA vaccines had the highest titre at D242 following their vaccine dose although Ad26. COV2. S (Janssen; hereafter referred to as Ad26) showed slower decay. For people who received BNT/BNT as their initial doses, a slower decay was also seen in the Ad26 and ChAd arms. The anti-spike IgG became significantly higher in the Ad26 arm compared to the BNT arm as early as 3 months following vaccination. Similar decay rates were seen between BNT and half-BNT; the geometric mean ratios ranged from 0.76 to 0.94 at different time points. The difference in decay rates between vaccines was similar for wild-type live virus-neutralising antibodies and that seen for anti-spike IgG. For cellular responses, the persistence was similar between study arms. CONCLUSIONS: Heterologous third doses with viral vector vaccines following two doses of mRNA achieve more durable humoral responses compared with three doses of mRNA vaccines. Lower doses of mRNA vaccines could be considered for future booster campaigns.


Asunto(s)
COVID-19 , Vacunas Virales , Femenino , Humanos , Anciano , Masculino , Vacunas contra la COVID-19 , Vacuna BNT162 , ChAdOx1 nCoV-19 , COVID-19/prevención & control , SARS-CoV-2 , Inmunidad , Reino Unido , Inmunoglobulina G , Anticuerpos Antivirales , Vacunación , Inmunogenicidad Vacunal
3.
Lancet Infect Dis ; 22(8): 1131-1141, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35550261

RESUMEN

BACKGROUND: Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19. METHODS: The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (anti-spike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing. FINDINGS: Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6-77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3-214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030-27 162), which increased to 37 460 ELU/mL (31 996-43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41-1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996-30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826-64 452), with a geometric mean fold change of 2·19 (1·90-2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37-14·32) and 15·90 (12·92-19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24-16·54] in the BNT162b2 group and 6·22 [3·90-9·92] in the mRNA-1273 group). INTERPRETATION: Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose. FUNDING: UK Vaccine Task Force and National Institute for Health Research.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Vacuna nCoV-2019 mRNA-1273 , Anciano , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , ChAdOx1 nCoV-19 , Femenino , Humanos , Inmunogenicidad Vacunal , Inmunoglobulina G , Masculino , Persona de Mediana Edad , SARS-CoV-2
4.
J Infect ; 84(6): 795-813, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35405168

RESUMEN

OBJECTIVES: To evaluate the persistence of immunogenicity three months after third dose boosters. METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study. RESULTS: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 µg) or BNT (30 µg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 µg) versus BNT (30 µg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. CONCLUSIONS: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.


Asunto(s)
COVID-19 , Vacunas Virales , Ad26COVS1 , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , ChAdOx1 nCoV-19 , Humanos , Inmunogenicidad Vacunal , Inmunoglobulina G , Persona de Mediana Edad , SARS-CoV-2 , Reino Unido , Vacunas de ARNm
5.
Lancet ; 398(10318): 2258-2276, 2021 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-34863358

RESUMEN

BACKGROUND: Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT). METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY)control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130. FINDINGS: Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44-61) in the younger age group and 76 years (73-78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41-59) in the younger age group and 78 years (75-82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5-2·3) in the half VLA group to 32·3 (24·8-42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7-1·6) for ChAd to 3·6 (2·4-5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0-1·5) in the half VLA group to 11·5 (9·4-14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7-1·6) for half VLA to 4·7 (3·1-7·1) for m1273. The results were similar between those aged 30-69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30-69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273. INTERPRETATION: All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination. FUNDING: UK Vaccine Taskforce and National Institute for Health Research.


Asunto(s)
Vacuna BNT162/administración & dosificación , COVID-19/prevención & control , ChAdOx1 nCoV-19/administración & dosificación , Inmunización Secundaria/métodos , Inmunogenicidad Vacunal , Adulto , Anciano , Anciano de 80 o más Años , Vacuna BNT162/inmunología , COVID-19/inmunología , ChAdOx1 nCoV-19/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Seguridad del Paciente , SARS-CoV-2 , Reino Unido
6.
Biosensors (Basel) ; 11(11)2021 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-34821633

RESUMEN

Recent advances suggest that miniaturised mid-infrared (MIR) devices could replace more time-consuming, laboratory-based techniques for clinical diagnostics. This work uses Fourier transform infrared spectroscopy to show that the MIR complex refractive index of whole blood varies across a range of haematocrit. This indicates that the use of an evanescent measurement is not sufficient to optically exclude the cellular content of blood in the MIR, as previously assumed. Here, spectral refractive index data is presented in two ways. First, it is given as whole blood with varying haematocrit. Second, it is given as the percentage error that haematocrit introduces to plasma. The maximum error in the effective plasma refractive index due to the haematocrit of healthy adults was 0.25% for the real part n and 11% for the imaginary part k. This implies that calibration measurements of haematocrit can be used to account for errors introduced by the cellular content, enabling plasma spectra and analyte concentrations to be indirectly calculated from a whole blood sample. This methodological advance is of clinical importance as plasma concentration of analytes such as drugs can be determined using MIR without the preprocessing of whole blood.


Asunto(s)
Hematócrito , Refractometría , Espectroscopía Infrarroja por Transformada de Fourier , Humanos , Preparaciones Farmacéuticas , Plasma
7.
BMJ Open ; 11(3): e044899, 2021 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-33737439

RESUMEN

OBJECTIVES: To describe the frequency of symptoms compatible with SARS-CoV-2 infection in immunocompromised children and young people in the UK during the SARS-CoV-2 pandemic. To describe patient/parent anxiety regarding SARS-CoV-2 infection in this cohort. DESIGN: A prospective observational cohort study. SETTING: 46 centres across the UK between 16 March and 4 July 2020. A weekly online questionnaire based on the International Severe Acute Respiratory and emerging Infections Consortium-WHO Case Report Form was used to collect participant reported data on symptoms, test results, National Health Service attendance, hospital admission and impact on daily life. PARTICIPANTS: 1490 immunocompromised children, defined as those requiring an annual influenza vaccination due to their underlying condition or medication. MAIN OUTCOME MEASURES: Incidence of SARS-CoV-2-like symptoms and patient/parent anxiety score. RESULTS: Over 16 weeks during the first wave of the pandemic, no SARS-CoV-2 infection was diagnosed in this large immunocompromised paediatric cohort (median age 11 years, 54.4% female). 110 symptomatic participants underwent a test for SARS-CoV-2; all were negative. 922 (67.4%) participants reported at least one symptom consistent with suspected SARS-CoV-2 infection over the study period. 476 (34.8%) reported three or more symptoms. The most frequently reported symptoms included joint pain, fatigue, headache, nausea and muscle pain. SARS-CoV-2 testing during this period was performed on admitted patients only. 137 participants had their medication suspended or changed during the study period due to assumed COVID-19 disease risk. 62% reported high levels of anxiety (scores of 7-10 out of 10) at the start of the study, with anxiety levels remaining high throughout the study period. CONCLUSIONS: Although symptoms related to SARS-CoV-2 infection in children were common, there were no positive tests in this large immunocompromised cohort. Symptom-based screening to facilitate early detection of SARS-CoV-2 infection may not be helpful in these individuals. Patient/parent anxiety about SARS-CoV-2 infection was high. TRIAL REGISTRATION NUMBER: NCT04382508.


Asunto(s)
COVID-19/epidemiología , Adolescente , Ansiedad , Prueba de COVID-19 , Niño , Femenino , Humanos , Masculino , Estudios Prospectivos , Medicina Estatal , Reino Unido/epidemiología
8.
Arch Dis Child Educ Pract Ed ; 106(4): 239-243, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33077533

RESUMEN

The deterioration of a previously stable preterm infant is a common scenario on the neonatal unit. The the most common bacterial causes of deterioration are nosocomial infections, such as coagulase-negative Staphylococcus and Staphylococcus aureus Non-infective conditions such as pulmonary haemorrhage, anaemia of prematurity and necrotising enterocolitis may also cause preterm infants to deteriorate. This case chronicles the unusual diagnostic journey of an infant born at 27+1 weeks who deteriorated at 26 days of life and did not respond to antimicrobial therapy as anticipated.


Asunto(s)
Enterocolitis Necrotizante , Enfermedades del Prematuro , Síndrome de Dificultad Respiratoria , Infecciones Estafilocócicas , Enterocolitis Necrotizante/diagnóstico , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/diagnóstico , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico
9.
Lancet ; 396(10267): 1979-1993, 2021 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-33220855

RESUMEN

BACKGROUND: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19 (AZD1222), in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older. METHODS: In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18-55 years, 56-69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 1010 virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18-55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56-69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5-6·5 × 1010 virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18-55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA80). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. FINDINGS: Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18-55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56-69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18-55 years group, 22 (73%) of 30 in the 56-69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18-55 years group, 23 (77%) in the 56-69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18-55 years, 20 713 arbitrary units [AU]/mL [IQR 13 898-33 550], n=39; 56-69 years, 16 170 AU/mL [10 233-40 353], n=26; and ≥70 years 17 561 AU/mL [9705-37 796], n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA80 at day 42 in the standard-dose groups: 18-55 years, 193 [IQR 113-238], n=39; 56-69 years, 144 [119-347], n=20; and ≥70 years, 161 [73-323], n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18-55 years: median 1187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841-2428], n=24; 56-69 years: 797 SFCs [383-1817], n=29; and ≥70 years: 977 SFCs [458-1914], n=48). INTERPRETATION: ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.


Asunto(s)
Vacunas contra la COVID-19/administración & dosificación , Inmunogenicidad Vacunal , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/farmacología , ChAdOx1 nCoV-19 , Femenino , Humanos , Inmunización Secundaria/efectos adversos , Inmunoglobulina G/sangre , Inmunoglobulina G/efectos de los fármacos , Masculino , Persona de Mediana Edad , SARS-CoV-2/efectos de los fármacos , Método Simple Ciego , Adulto Joven
10.
Int J Pediatr Otorhinolaryngol ; 132: 109905, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32035348

RESUMEN

INTRODUCTION: Idiopathic facial nerve palsy (FNP) is an uncommon but important presentation in children, with Lyme disease known to be a common cause. The UK county of Hampshire is a high incidence area of Lyme disease. We conducted a retrospective review of the investigation and management of paediatric FNP at a large University hospital, including serologic testing and treatment of Lyme disease. METHODS: We conducted a retrospective chart review of children under 18 presenting between January 1st, 2010 and December 31st, 2017 with a diagnosis of FNP. Patients with clear non-Lyme aetiology at presentation were excluded. Data was collected on demographics, initial presentation, investigations including Lyme serology, and management. RESULTS: A total of 93 children were identified, with an even proportion of male to female and median age 9.3 years (IQR 4.6-12 years). A history of rash was present in 5.4%, tick bite in 14% and recent travel to, or residence in the New Forest in 22.6%. Lyme serology was performed in 81.7% of patients, of which 29% were positive. Antibiotics were prescribed for 73.1% of patients, oral steroids for 44% and aciclovir for 17.2%. CONCLUSION: Lyme disease is a significant cause of FNP in this endemic area of the UK, and there was a large degree of variability in management prior to national guideline publication. Areas with endemic Lyme disease should consider introducing local guidelines supporting routine investigation and management for FNP, including empiric treatment for Lyme disease in accordance with NICE guidelines to improve care and reduce variability.


Asunto(s)
Parálisis de Bell/etiología , Enfermedad de Lyme/complicaciones , Parálisis de Bell/epidemiología , Niño , Preescolar , Enfermedades Endémicas , Femenino , Humanos , Enfermedad de Lyme/diagnóstico , Enfermedad de Lyme/epidemiología , Masculino , Estudios Retrospectivos , Reino Unido/epidemiología
11.
Acta Paediatr ; 101(5): 524-7, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22233229

RESUMEN

AIM: Recent data are scarce on the provision of home parenteral nutrition (HPN) in children from the UK but would help to commission intestinal failure services. Our aim was to describe 10 years of HPN experience in our centre, which serves a population of 650,000 children. METHODS: Outcome and complication data were collected retrospectively from hospital records of children receiving HPN from April 2001. Data from other centres were used to compare complications and outcomes in the provision of HPN. RESULTS: Nineteen children (12 females) received 10,213 days (28 years) of HPN. In this group, incidence of blood culture positive sepsis was four episodes/1000 days PN. Two children had early intestinal failure-associated liver disease. Of the 19, seven still receive HPN at our centre, six survived PN, three were transferred to other services while still on HPN and three died. CONCLUSION: Outcome and complication data for HPN from a single UK regional paediatric centre are similar to larger centres. These data provide recent evidence of the disease burden of HPN, which are important for the commissioning of intestinal failure services.


Asunto(s)
Nutrición Parenteral en el Domicilio/estadística & datos numéricos , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Nutrición Parenteral en el Domicilio/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
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