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1.
Pediatr Infect Dis J ; 42(6): 496-502, 2023 06 01.
Article in English | MEDLINE | ID: covidwho-2248375

ABSTRACT

BACKGROUND: Antibodies are a measure of immunity after primary infection, which may help protect against further SARS-CoV-2 infections. They may also provide some cross-protection against SARS-CoV-2 variants. There are limited data on antibody persistence and, especially, cross-reactivity against different SARS-CoV-2 variants after primary infection in children. METHODS: We initiated enhanced surveillance in 18 secondary schools to monitor SARS-CoV-2 infection and transmission in September 2020. Students and Staff provided longitudinal blood samples to test for variant-specific SARS-CoV-2 antibodies using in-house receptor binding domain assays. We recruited 1189 students and 1020 staff; 160 (97 students, 63 staff) were SARS-CoV-2 nucleocapsid-antibody positive at baseline and had sufficient serum for further analysis. RESULTS: Most participants developed sustained antibodies against their infecting [wild-type (WT)] strain as well as cross-reactive antibodies against the Alpha, Beta and Delta variants but at lower titers than WT. Staff had significantly lower antibodies titers against WT as cross-reactive antibodies against the Alpha, Beta and Delta variants than students (all P < 0.01). In participants with sufficient sera, only 2.3% (1/43) students and 17.2% (5/29) staff had cross-reactive antibodies against the Omicron variant; they also had higher antibody titers against WT (3042.5; 95% confidence interval: 769.0-12,036.2) than those who did not have cross-reactive antibodies against the Omicron variant (680.7; 534.2-867.4). CONCLUSIONS: We found very high rates of antibody persistence after primary infection with WT in students and staff. Infection with WT induced cross-reactive antibodies against Alpha, Beta and Delta variants, but not Omicron. Primary infection with WT may not be cross-protective against the Omicron variant.


Subject(s)
COVID-19 , SARS-CoV-2 , Child , Adolescent , Humans , Prospective Studies , Antibodies, Viral , Antibodies, Neutralizing
2.
JMIR Public Health Surveill ; 8(12): e39141, 2022 12 19.
Article in English | MEDLINE | ID: covidwho-2198102

ABSTRACT

BACKGROUND: The Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) is one of Europe's oldest sentinel systems, working with the UK Health Security Agency (UKHSA) and its predecessor bodies for 55 years. Its surveillance report now runs twice weekly, supplemented by online observatories. In addition to conducting sentinel surveillance from a nationally representative group of practices, the RSC is now also providing data for syndromic surveillance. OBJECTIVE: The aim of this study was to describe the cohort profile at the start of the 2021-2022 surveillance season and recent changes to our surveillance practice. METHODS: The RSC's pseudonymized primary care data, linked to hospital and other data, are held in the Oxford-RCGP Clinical Informatics Digital Hub, a Trusted Research Environment. We describe the RSC's cohort profile as of September 2021, divided into a Primary Care Sentinel Cohort (PCSC)-collecting virological and serological specimens-and a larger group of syndromic surveillance general practices (SSGPs). We report changes to our sampling strategy that brings the RSC into alignment with European Centre for Disease Control guidance and then compare our cohort's sociodemographic characteristics with Office for National Statistics data. We further describe influenza and COVID-19 vaccine coverage for the 2020-2021 season (week 40 of 2020 to week 39 of 2021), with the latter differentiated by vaccine brand. Finally, we report COVID-19-related outcomes in terms of hospitalization, intensive care unit (ICU) admission, and death. RESULTS: As a response to COVID-19, the RSC grew from just over 500 PCSC practices in 2019 to 1879 practices in 2021 (PCSC, n=938; SSGP, n=1203). This represents 28.6% of English general practices and 30.59% (17,299,780/56,550,136) of the population. In the reporting period, the PCSC collected >8000 virology and >23,000 serology samples. The RSC population was broadly representative of the national population in terms of age, gender, ethnicity, National Health Service Region, socioeconomic status, obesity, and smoking habit. The RSC captured vaccine coverage data for influenza (n=5.4 million) and COVID-19, reporting dose one (n=11.9 million), two (n=11 million), and three (n=0.4 million) for the latter as well as brand-specific uptake data (AstraZeneca vaccine, n=11.6 million; Pfizer, n=10.8 million; and Moderna, n=0.7 million). The median (IQR) number of COVID-19 hospitalizations and ICU admissions was 1181 (559-1559) and 115 (50-174) per week, respectively. CONCLUSIONS: The RSC is broadly representative of the national population; its PCSC is geographically representative and its SSGPs are newly supporting UKHSA syndromic surveillance efforts. The network captures vaccine coverage and has expanded from reporting primary care attendances to providing data on onward hospital outcomes and deaths. The challenge remains to increase virological and serological sampling to monitor the effectiveness and waning of all vaccines available in a timely manner.


Subject(s)
COVID-19 , General Practitioners , Influenza Vaccines , Influenza, Human , Humans , Influenza, Human/epidemiology , COVID-19 Vaccines , State Medicine , Vaccination , United Kingdom/epidemiology
3.
J Infect ; 85(5): 545-556, 2022 11.
Article in English | MEDLINE | ID: covidwho-2007862

ABSTRACT

OBJECTIVES: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. METHODS: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. RESULTS: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001-0·31) and LV-N Alpha (OR 0·07, CI 0·009-0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03-0·64) and Alpha (0·06, CI 0·008-0·40). CONCLUSIONS: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect. TRIAL REGISTRATION NUMBER: ISRCTN11041050.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/prevention & control , Case-Control Studies , Humans , Reinfection/prevention & control , Vaccination
4.
Front Immunol ; 13: 882515, 2022.
Article in English | MEDLINE | ID: covidwho-1903016

ABSTRACT

Children and adolescents generally experience mild COVID-19. However, those with underlying physical health conditions are at a significantly increased risk of severe disease. Here, we present a comprehensive analysis of antibody and cellular responses in adolescents with severe neuro-disabilities who received COVID-19 vaccination with either ChAdOx1 (n=6) or an mRNA vaccine (mRNA-1273, n=8, BNT162b2, n=1). Strong immune responses were observed after vaccination and antibody levels and neutralisation titres were both higher after two doses. Both measures were also higher after mRNA vaccination and were further enhanced by prior natural infection where one vaccine dose was sufficient to generate peak antibody response. Robust T-cell responses were generated after dual vaccination and were also higher following mRNA vaccination. Early T-cells were characterised by a dominant effector-memory CD4+ T-cell population with a type-1 cytokine signature with additional production of IL-10. Antibody levels were well-maintained for at least 3 months after vaccination and 3 of 4 donors showed measurable neutralisation titres against the Omicron variant. T-cell responses also remained robust, with generation of a central/stem cell memory pool and showed strong reactivity against Omicron spike. These data demonstrate that COVID-19 vaccines display strong immunogenicity in adolescents and that dual vaccination, or single vaccination following prior infection, generate higher immune responses than seen after natural infection and develop activity against Omicron. Initial evidence suggests that mRNA vaccination elicits stronger immune responses than adenoviral delivery, although the latter is also higher than seen in adult populations. COVID-19 vaccines are therefore highly immunogenic in high-risk adolescents and dual vaccination might be able to provide relative protection against the Omicron variant that is currently globally dominant.


Subject(s)
COVID-19 Vaccines , COVID-19 , 2019-nCoV Vaccine mRNA-1273 , Adolescent , Adult , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Child , Humans , RNA, Messenger , SARS-CoV-2 , Vaccination , Vaccines, Synthetic , mRNA Vaccines
5.
J Infect ; 84(5): 675-683, 2022 05.
Article in English | MEDLINE | ID: covidwho-1788130

ABSTRACT

Background COVID-19 vaccines approved in the UK are highly effective in general population cohorts, however, data on effectiveness amongst individuals with clinical conditions that place them at increased risk of severe disease are limited. Methods We used GP electronic health record data, sentinel virology swabbing and antibody testing within a cohort of 712 general practices across England to estimate vaccine antibody response and vaccine effectiveness against medically attended COVID-19 amongst individuals in clinical risk groups using cohort and test-negative case control designs. Findings There was no reduction in S-antibody positivity in most clinical risk groups, however reduced S-antibody positivity and response was significant in the immunosuppressed group. Reduced vaccine effectiveness against clinical disease was also noted in the immunosuppressed group; after a second dose, effectiveness was moderate (Pfizer: 59.6%, 95%CI 18.0-80.1%; AstraZeneca 60.0%, 95%CI -63.6-90.2%). Interpretation In most clinical risk groups, immune response to primary vaccination was maintained and high levels of vaccine effectiveness were seen. Reduced antibody response and vaccine effectiveness were seen after 1 dose of vaccine amongst a broad immunosuppressed group, and second dose vaccine effectiveness was moderate. These findings support maximising coverage in immunosuppressed individuals and the policy of prioritisation of this group for third doses.


Subject(s)
COVID-19 Vaccines , COVID-19 , BNT162 Vaccine , COVID-19/prevention & control , ChAdOx1 nCoV-19 , Humans , Immunity , SARS-CoV-2 , Vaccine Efficacy
6.
J Infect ; 84(6): 814-824, 2022 06.
Article in English | MEDLINE | ID: covidwho-1778314

ABSTRACT

OBJECTIVES: To monitor changes in seroprevalence of SARS-CoV-2 antibodies in populations over time and between different demographic groups. METHODS: A subset of practices in the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network provided serum samples, collected when volunteer patients had routine blood tests. We tested these samples for SARS-CoV-2 antibodies using Abbott (Chicago, USA), Roche (Basel, Switzerland) and/or Euroimmun (Luebeck, Germany) assays, and linked the results to the patients' primary care computerised medical records. We report seropositivity by region and age group, and additionally examined the effects of gender, ethnicity, deprivation, rurality, shielding recommendation and smoking status. RESULTS: We estimated seropositivity from patients aged 18-100 years old, which ranged from 4.1% (95% CI 3.1-5.3%) to 8.9% (95% CI 7.8-10.2%) across the different assays and time periods. We found higher Euroimmun seropositivity in younger age groups, people of Black and Asian ethnicity (compared to white), major conurbations, and non-smokers. We did not observe any significant effect by region, gender, deprivation, or shielding recommendation. CONCLUSIONS: Our results suggest that prior to the vaccination programme, most of the population remained unexposed to SARS-CoV-2.


Subject(s)
COVID-19 , General Practitioners , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral , COVID-19/epidemiology , England/epidemiology , Humans , Middle Aged , Primary Health Care , SARS-CoV-2 , Seroepidemiologic Studies , Young Adult
7.
Microbiol Spectr ; 10(1): e0228921, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1702730

ABSTRACT

In March 2020, the Rare and Imported Pathogens Laboratory at the UK Health Security Agency (UKHSA) (formerly Public Health England [PHE]) Porton Down, was tasked by the Department of Health and Social Care with setting up a national surveillance laboratory facility to study SARS-CoV-2 antibody responses and population-level sero-surveillance in response to the growing SARS-CoV-2 outbreak. In the following 12 months, the laboratory tested more than 160,000 samples, facilitating a wide range of research and informing UKHSA, DHSC, and UK government policy. Here we describe the implementation and use of the Euroimmun anti-SARS-CoV-2 IgG assay and provide an extended evaluation of its performance. We present a markedly improved overall sensitivity of 91.39% (≥14 days 92.74%, ≥21 days 93.59%) compared to our small-scale early study, and a specificity of 98.56%. In addition, we detail extended characteristics of the Euroimmun assay: intra- and interassay precision, correlation to neutralization, and assay linearity. IMPORTANCE Serology assays have been useful in determining those with previous SARS-CoV-2 infection in a wide range of research and serosurveillance projects. However, assays vary in their sensitivity at detecting SARS-CoV-2 antibodies. Here, we detail an extended evaluation and characterization of the Euroimmun anti-SARS-CoV-2 IgG assay, one that has been widely used within the United Kingdom on over 160,000 samples to date.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/blood , Immunoglobulin G/blood , SARS-CoV-2/immunology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Humans , Public Health , Reagent Kits, Diagnostic , SARS-CoV-2/genetics , Sensitivity and Specificity , United Kingdom/epidemiology
8.
EClinicalMedicine ; 45: 101319, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1704577

ABSTRACT

BACKGROUND: The role of educational settings in SARS-CoV-2 infection and transmission remains controversial. We investigated SARS-CoV-2 infection, seroprevalence, and seroconversion rates in secondary schools during the 2020/21 academic year, which included the emergence of the more transmissible alpha and delta variants, in England. METHODS: The UK Health Security Agency (UKHSA) initiated prospective surveillance in 18 urban English secondary schools. Participants had nasal swabs for SARS-CoV-2 RT-PCR and blood sampling for SARS-CoV-2 nucleoprotein and spike protein antibodies at the start (Round 1: September-October 2020) and end (Round 2: December 2020) of the autumn term, when schools reopened after national lockdown was imposed in January 2021 (Round 3: March-April 2021), and end of the academic year (Round 4: May-July 2021). FINDINGS: We enrolled 2314 participants (1277 students, 1037 staff; one participant had missing data for PCR testing). In-school testing identified 31 PCR-positive participants (20 students, 11 staff). Another 247 confirmed cases (112 students, 135 staff) were identified after linkage with national surveillance data, giving an overall positivity rate of 12.0% (278/2313; staff: 14.1%, 146/1037 vs students: 10.3%, 132/1276; p = 0.006). Trends were similar to national infection data. Nucleoprotein-antibody seroprevalence increased for students and staff between Rounds 1 and 3 but were similar between Rounds 3 and 4, when the delta variant was the dominant circulating strain. Overall, Nucleoprotein-antibody seroconversion was 18.4% (137/744) in staff and 18.8% (146/778) in students, while Spike-antibody seroconversion was higher in staff (72.8%, 525/721) than students (21.3%, 163/764) because of vaccination. INTERPRETATION: SARS-CoV-2 infection rates in secondary schools remained low when community infection rates were low, even as the delta variant was emerging in England. FUNDING: This study was funded by the UK Department of Health and Social Care.

9.
N Engl J Med ; 386(13): 1207-1220, 2022 03 31.
Article in English | MEDLINE | ID: covidwho-1692473

ABSTRACT

BACKGROUND: The duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters. METHODS: We investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (≤10 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2. RESULTS: Of 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 95% of the participants had received two doses (78% had received BNT162b2 vaccine [Pfizer-BioNTech] with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine [AstraZeneca]). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval [CI], 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) - considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously. CONCLUSIONS: Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection. (Funded by the U.K. Health Security Agency and others; ISRCTN Registry number, ISRCTN11041050.).


Subject(s)
Adaptive Immunity , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Adaptive Immunity/immunology , Asymptomatic Diseases , BNT162 Vaccine/therapeutic use , COVID-19/diagnosis , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Nucleic Acid Testing , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , ChAdOx1 nCoV-19/therapeutic use , Health Personnel , Humans , Prospective Studies , United Kingdom , Vaccination/methods , Vaccine Efficacy
10.
Euro Surveill ; 27(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1613512

ABSTRACT

Serum samples were collected pre- and post-booster vaccination with Comirnaty in 626 participants (aged ≥ 50 years) who had received two Comirnaty doses < 30 days apart, two Comirnaty doses ≥ 30 days apart or two Vaxzevria doses ≥ 30 days apart. Irrespective of primary vaccine type or schedule, spike antibody GMTs peaked 2-4 weeks after second dose, fell significantly ≤ 38 weeks later and rose above primary immunisation GMTs 2-4 weeks post-booster. Higher post-booster responses were observed with a longer interval between primary immunisation and boosting.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , London , SARS-CoV-2 , United Kingdom
11.
Nat Immunol ; 23(1): 40-49, 2022 01.
Article in English | MEDLINE | ID: covidwho-1585824

ABSTRACT

SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3-11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.


Subject(s)
Antibodies, Viral/immunology , Coronavirus 229E, Human/immunology , Coronavirus OC43, Human/immunology , Cross Protection/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adaptive Immunity/immunology , Adult , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Child , Child, Preschool , Cross Reactions/immunology , Humans
12.
Nat Commun ; 12(1): 7217, 2021 12 10.
Article in English | MEDLINE | ID: covidwho-1565716

ABSTRACT

The UK prioritised delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval between doses up to 12 weeks. In 750 participants aged 50-89 years, we here compare serological responses after BNT162b2 and AZD1222 vaccination with varying dose intervals, and evaluate these against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. We show that antibody levels 14-35 days after dose two are higher in BNT162b2 recipients with an extended vaccine interval (65-84 days) compared with those vaccinated with a standard (19-29 days) interval. Following the extended schedule, antibody levels were 6-fold higher at 14-35 days post dose 2 for BNT162b2 than AZD1222. For both vaccines, VE was higher across all age-groups from 14 days after dose two compared to one dose, but the magnitude varied with dose interval. Higher dose two VE was observed with >6 week interval between BNT162b2 doses compared to the standard schedule. Our findings suggest higher effectiveness against infection using an extended vaccine schedule. Given global vaccine constraints these results are relevant to policymakers.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunization Schedule , Vaccine Efficacy , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibody Formation , BNT162 Vaccine , COVID-19 Vaccines/administration & dosage , ChAdOx1 nCoV-19 , England , Female , Humans , Male , Middle Aged
14.
J Infect ; 83(5): 573-580, 2021 11.
Article in English | MEDLINE | ID: covidwho-1527750

ABSTRACT

OBJECTIVES: We assessed SARS-CoV-2 infection, seroprevalence and seroconversion in students and staff when secondary schools reopened in March 2021. METHODS: We initiated SARS-CoV-2 surveillance in 18 secondary schools across six regions in September 2020. Participants provided nasal swabs for RT-PCR and blood samples for SARS-CoV-2 antibodies at the beginning (September 2020) and end (December 2020) of the autumn term and at the start of the spring term (March 2021). FINDINGS: In March 2021, 1895 participants (1100 students:795 staff) were tested; 5.6% (61/1094) students and 4.4% (35/792) staff had laboratory-confirmed SARS-CoV-2 infection from December 2020-March 2021. Nucleoprotein-antibody seroprevalence was 36.3% (370/1018) in students and 31.9% (245/769) in staff, while spike-antibody prevalence was 39.5% (402/1018) and 59.8% (459/769), respectively, similar to regional community seroprevalence. Between December 2020 and March 2021, 14.8% (97/656; 95%CI: 12.2-17.7) students and 10.0% (59/590; 95%CI: 7.7-12.7) staff seroconverted. Weekly seroconversion rates were similar from September to December 2020 (8.0/1000) and from December 2020 to March 2021 (7.9/1000; students: 9.3/1,000; staff: 6.3/1,000). INTERPRETATION: By March 2021, a third of secondary school students and staff had evidence of prior infection based on N-antibody seropositivity, and an additional third of staff had evidence of vaccine-induced immunity based on S-antibody seropositivity.


Subject(s)
COVID-19 , SARS-CoV-2 , Seroconversion , Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/immunology , England/epidemiology , Humans , Prospective Studies , Schools , Seroepidemiologic Studies , Students
15.
EClinicalMedicine ; 41: 101150, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1446584

ABSTRACT

BACKGROUND: Prospective, longitudinal SARS-CoV-2 sero-surveillance in schools across England was initiated after the first national lockdown, allowing comparison of child and adult antibody responses over time. METHODS: Prospective active serological surveillance in 46 primary schools in England tested for SARS-CoV-2 antibodies during June, July and December 2020. Samples were tested for nucleocapsid (N) and receptor binding domain (RBD) antibodies, to estimate antibody persistence at least 6 months after infection, and for the correlation of N, RBD and live virus neutralising activity. FINDINGS: In June 2020, 1,344 staff and 835 students were tested. Overall, 11.5% (95%CI: 9.4-13.9) and 11.3% (95%CI: 9.2-13.6; p = 0.88) of students had nucleoprotein and RBD antibodies, compared to 15.6% (95%CI: 13.7-17.6) and 15.3% (95%CI: 13.4-17.3; p = 0.83) of staff. Live virus neutralising activity was detected in 79.8% (n = 71/89) of nucleocapsid and 85.5% (71/83) of RBD antibody positive children. RBD antibodies correlated more strongly with neutralising antibodies (rs=0.7527; p<0.0001) than nucleocapsid antibodies (rs=0.3698; p<0.0001). A median of 24.4 weeks later, 58.2% (107/184) participants had nucleocapsid antibody seroreversion, compared to 20.9% (33/158) for RBD (p<0.001). Similar seroreversion rates were observed between staff and students for nucleocapsid (p = 0.26) and RBD-antibodies (p = 0.43). Nucleocapsid and RBD antibody quantitative results were significantly lower in staff compared to students (p = 0.028 and <0.0001 respectively) at baseline, but not at 24 weeks (p = 0.16 and p = 0.37, respectively). INTERPRETATION: The immune response in children following SARS-CoV-2 infection was robust and sustained (>6 months) but further work is required to understand the extent to which this protects against reinfection.

17.
Nat Immunol ; 22(5): 620-626, 2021 05.
Article in English | MEDLINE | ID: covidwho-1387432

ABSTRACT

The immune response to SARS-CoV-2 is critical in controlling disease, but there is concern that waning immunity may predispose to reinfection. We analyzed the magnitude and phenotype of the SARS-CoV-2-specific T cell response in 100 donors at 6 months following infection. T cell responses were present by ELISPOT and/or intracellular cytokine staining analysis in all donors and characterized by predominant CD4+ T cell responses with strong interleukin (IL)-2 cytokine expression. Median T cell responses were 50% higher in donors who had experienced a symptomatic infection, indicating that the severity of primary infection establishes a 'set point' for cellular immunity. T cell responses to spike and nucleoprotein/membrane proteins were correlated with peak antibody levels. Furthermore, higher levels of nucleoprotein-specific T cells were associated with preservation of nucleoprotein-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T cell responses are retained at 6 months following infection.


Subject(s)
Antigens, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immunity, Cellular , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/virology , COVID-19/blood , COVID-19/virology , Female , Host-Pathogen Interactions , Humans , Interleukin-2/blood , Male , Middle Aged , Phenotype , SARS-CoV-2/pathogenicity , Time Factors , Young Adult
18.
Emerg Infect Dis ; 27(7): 1795-1801, 2021 07.
Article in English | MEDLINE | ID: covidwho-1278355

ABSTRACT

We describe results of testing blood donors in London, UK, for severe acute respiratory disease coronavirus 2 (SARS-CoV-2) IgG before and after lockdown measures. Anonymized samples from donors 17-69 years of age were tested using 3 assays: Euroimmun IgG, Abbott IgG, and an immunoglobulin receptor-binding domain assay developed by Public Health England. Seroprevalence increased from 3.0% prelockdown (week 13, beginning March 23, 2020) to 10.4% during lockdown (weeks 15-16) and 12.3% postlockdown (week 18) by the Abbott assay. Estimates were 2.9% prelockdown, 9.9% during lockdown, and 13.0% postlockdown by the Euroimmun assay and 3.5% prelockdown, 11.8% during lockdown, and 14.1% postlockdown by the receptor-binding domain assay. By early May 2020, nearly 1 in 7 donors had evidence of past SARS-CoV-2 infection. Combining results from the Abbott and Euroimmun assays increased seroprevalence by 1.6%, 2.3%, and 0.6% at the 3 timepoints compared with Euroimmun alone, demonstrating the value of using multiple assays.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Blood Donors , Communicable Disease Control , England , Humans , Immunoglobulin G , London/epidemiology , Public Health , Sensitivity and Specificity , Seroepidemiologic Studies , United Kingdom
19.
EClinicalMedicine ; 37: 100948, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1272390

ABSTRACT

BACKGROUND: Older children have higher SARS-CoV-2 infection rates than younger children. We investigated SARS-CoV-2 infection, seroprevalence and seroconversion rates in staff and students following the full reopening of all secondary schools in England. METHODS: Public Health England (PHE) invited secondary schools in six regions (East and West London, Hertfordshire, Derbyshire, Manchester and Birmingham) to participate in SARS-CoV-2 surveillance during the 2020/21 academic year. Participants had nasal swabs for RT-PCR and blood samples for SARS-CoV-2 antibodies at the beginning (September 2020) and end (December 2020) of the autumn term. Multivariable logistic regression was used to assess independent risk factors for seropositivity and seroconversion. FINDINGS: Eighteen schools in six regions enrolled 2,209 participants, including 1,189 (53.8%) students and 1,020 (46.2%) staff. SARS-CoV-2 infection rates were not significantly different between students and staff in round one (5/948; [0.53%] vs. 2/876 [0.23%]; p = 0.46) or round two (10/948 [1.05%] vs. 7/886 [0.79%]; p = 0.63), and similar to national prevalence. None of four and 7/15 (47%) sequenced strains in rounds 1 and 2 were the highly transmissible SARS-CoV-2 B.1.1.7 variant. In round 1, antibody seropositivity was higher in students than staff (114/893 [12.8%] vs. 79/861 [9.2%]; p = 0.016), but similar in round 2 (117/893 [13.1%] vs.117/872 [13.3%]; p = 0.85), comparable to local community seroprevalence. Between the two rounds, 8.7% (57/652) staff and 6.6% (36/549) students seroconverted (p = 0.16). INTERPRETATION: In secondary schools, SARS-CoV-2 infection, seropositivity and seroconversion rates were similar in staff and students, and comparable to local community rates. Ongoing surveillance will be important for monitoring the impact of new variants in educational settings.

20.
J Infect ; 83(2): 237-279, 2021 08.
Article in English | MEDLINE | ID: covidwho-1225296

ABSTRACT

The COVID-19 vaccination programme commenced in England on 8th December 2020 primarily based on age; by 7th March 2021 approximately 93% of the English population aged 70+ years had received at least 1 dose of either the Pfizer BioNTech or AstraZeneca vaccines. Using a nucleoprotein assay that detects antibodies following natural infection only and a spike assay that detects infection and vaccine-induced responses, we aim to describe the impact of vaccination on SARS-CoV-2 antibody prevalence in English blood donors.


Subject(s)
COVID-19 Vaccines , COVID-19 , Aged , Antibody Formation , Blood Donors , England/epidemiology , Health Personnel , Humans , RNA, Messenger , SARS-CoV-2 , Seroepidemiologic Studies , Vaccination
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