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In contrast to the increasing levels of high avidity S antibody measured by the Roche assay in the first 6 months following natural infection, marked waning is seen post 2 or 3 doses of vaccine. Although the kinetics differ between those with vaccine-induced immunity compared to those infected prior to vaccination (hybrid immunity), waning rates appear to be similar following 2 or 3 doses of vaccine. These data should allow countries to optimise the timing of future doses of vaccine.
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BackgroundThere are limited data on immune responses to heterologous COVID-19 immunisation schedules, especially following an extended [≥]12-week interval between doses. MethodsSARS-CoV-2 infection-naive and previously-infected adults receiving ChAd-BNT (ChAdOx1 nCoV-19, AstraZeneca followed by BNT162b2, Pfizer-BioNTech) or BNT-ChAd as part of the UK national immunisation programme provided blood samples at 30 days and 12 weeks after their second dose. Geometric mean concentrations (GMC) of anti-SARS-CoV-2 spike (S-antibody) and nucleoprotein (N-antibody) IgG antibodies and geometric mean ratios (GMR) were compared with a contemporaneous cohort receiving homologous ChAd-ChAd or BNT-BNT. ResultsDuring March-October 2021, 75,827 individuals were identified as having received heterologous vaccination, 9,489 invited to participate, 1,836 responded (19.3%) and 656 were eligible. In previously-uninfected adults, S-antibody GMC at 30 days post-second dose were lowest for ChAd-ChAd (862 [95%CI, 694 - 1069]) and significantly higher for ChAd-BNT (6233 [5522-7035]; GMR 6.29; [5.04-7.85]; p<0.001), BNT-ChAd (4776 [4066-5610]; GMR 4.55 [3.56-5.81]; p<0.001) and BNT-BNT (5377 [4596-6289]; GMR 5.66 [4.49-7.15]; p<0.001). By 12 weeks after dose two, S-antibody GMC had declined in all groups and remained significantly lower for ChAd-ChAd compared to ChAd-BNT (GMR 5.12 [3.79-6.92]; p<0.001), BNT-ChAd (GMR 4.1 [2.96-5.69]; p<0.001) and BNT-BNT (GMR 6.06 [4.32-8.50]; p<0.001). Previously infected adults had higher S-antibody GMC compared to infection-naive adults at all time-points and with all vaccine schedules. ConclusionsThese real-world findings demonstrate heterologous schedules with adenoviral-vector and mRNA vaccines are highly immunogenic and may be recommended after a serious adverse reaction to one vaccine product, or to increase programmatic flexibility where vaccine supplies are constrained. O_TEXTBOXWhat is already known?PubMed was searched with the terms "COVID-19 Vaccine" and "heterologous" to identify publications relating to heterologous immunisation schedules with adenoviral-vector and mRNA vaccines from 01 January 2020 until 30 November 2021. Following early reports of vaccine-induced thrombocytosis and thrombocytopenia (VITT) after the first dose of ChAd (ChAdOx1 nCoV-19), several studies reported significantly higher antibody levels, with robust neutralizing activity and cellular immune responses, in adults receiving a heterologous ChAd-mRNA schedule compared to those receiving ChAd-ChAd. Few studies, however, have compared antibody responses after both heterologous schedules (ChAd-mRNA and mRNA-ChAd) with both homologous schedules (ChAd-ChAd and mRNA-mRNA). One UK study (COMCOV) compared all four ChAd and BNT162b2 Pfizer-BioNTech (BNT; mRNA) combinations given four weeks apart and reported very high antibody and T-cell responses four weeks after the second dose for all four schedules. What are the new findings?We used the national immunisation register to identify adults who received a heterologous vaccine schedule as part of the national immunisation programme in England and collected blood samples to measure SARS-CoV-2 antibody responses after vaccination. We found that both heterologous schedules (ChAd-BNT and BNT-ChAd) provided superior antibody responses compared to ChAd-ChAd and similar responses to BNT-BNT at 30 days and 12 weeks after second vaccine dose. ChAd-BNT induced higher antibody levels then BNT-ChAd at both timepoints. Antibody responses after vaccination were much higher in previously infected individuals, irrespective of their immunisation schedule. A recent Swedish population-based study reported higher vaccine effectiveness against symptomatic disease with ChAd-BNT than ChAd-ChAd providing real-world confirmation of improved protection with heterologous schedules. What do the new findings imply?Our findings add to the growing body of evidence showing high antibody responses following heterologous vaccination schedules with ChAd and BNT, along with robust antibody neutralising activity and cellular responses, especially when compared to ChAd-ChAd. Given that globally COVID-19 vaccine demand far exceeds vaccine supply, these results have important implications for the future deployment of COVID-19 vaccine programmes; particularly where it is logistically and/or operationally difficult to administer two doses of the same vaccine product. C_TEXTBOX
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BackgroundThe role of educational settings on SARS-CoV-2 infection and transmission remains controversial. We investigated SARS-CoV-2 infection, seroprevalence and seroconversions rates in secondary schools during the 2020/21 academic year, which included the emergence of the more transmissible Alpha and Delta variants, in England. MethodsThe 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 2021) of the autumn term, when schools reopened after national lockdown was imposed in January 2021 (Round 3: March-April) and end of the academic year (Round 4: May-July). FindingsWe enrolled 2,314 participants (1277 students, 1037 staff). 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). Nucleoprotein-antibody seroprevalence increased for students and staff between Rounds 1-3 but changed little in Round 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. InterpretationSARS-CoV-2 infection and transmission in secondary schools remained low when community infection rates were low because of national lockdown, even after the emergence of the Delta variant FundingDHSC
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BackgroundReinfection after primary SARS-CoV-2 infection is uncommon in adults, but little is known about the risks, characteristics, severity or outcomes of reinfection in children. MethodsWe used national SARS-CoV-2 testing data in England to estimate the risk of reinfection [≥]90 days after primary infection from 01 January 2020 to 31 July 2021, which encompassed both the Alpha and Delta waves in England. Disease severity was assessed by linking reinfection cases to national hospitalisation, intensive care admission and death registrations datasets. FindingsReinfection rates closely followed community infection rates, with a small peak during the Alpha wave and a larger peak during the Delta wave. In children aged [≤]16 years, there were 688,418 primary infections and 2,343 reinfections. The overall reinfection rate was 66{middle dot}88/100,000 population, being higher in adults (72.53/100,000) than in children (21{middle dot}53/100,000). Reinfection rates after primary infection were 0{middle dot}68% overall, 0{middle dot}73% in adults and 0{middle dot}34% in children. Of the 109 reinfections in children admitted to hospital, 78 (72%) had underlying comorbidities. Hospitalisation rates were similar for the first (64/2343, 2{middle dot}73%) and second episode (57/2343, 2{middle dot}43%). Intensive care admission was rare after primary infection (n=7) or reinfection (n=4), mainly in children with comorbidities. 44 deaths occurred after primary infection within 28 days of diagnosis (44/688,418, 0{middle dot}01%), none after possible reinfections. InterpretationThe risk of SARS-CoV-2 reinfection is strongly related to exposure due to community infection rates, especially during the Delta variant wave. Children had a lower risk of reinfection than adults, but reinfections were not associated with more severe disease or fatal outcomes. FundingPHE/UKHSA Research in ContextO_ST_ABSEvidence Before this studyC_ST_ABSWe searched PubMed with the terms "COVID-19" or "SARS-CoV-2" with "reinfection" to identify publications relating to SARS-CoV-2 reinfections from 01 January until 15 November 2021. There were few publications relating to SARS-CoV-2 reinfections, and these primarily related to adults. Published studies reported very low rates of reinfection during the first few months after primary infection in adults. COVID-19 vaccines provide effective immune protection against SARS-CoV-2 infection, but recent studies have reported increasing risk of breakthrough infection with time since primary vaccination due to waning immunity. Several SARS-CoV-2 variants, including the beta, gamma and delta variants have been shown to partially evade immunity after natural infection and vaccination, potentially increasing the risk of reinfections and breakthrough infections, respectively. Data on reinfections in children are lacking and restricted mainly to case reports in immunocompromised children. Added Value of This StudyWe used national SARS-CoV-2 testing data during the first 19 months of the pandemic to estimate the risk of reinfection in children compared to adults during a period that encompassed both the Alpha and the Delta variant waves in England. We found that the risk of reinfection correlated with the risk of SARS-CoV-2 exposure and therefore, closely reflected community infection rates, with most reinfections occurring during the Delta variant wave. Whilst acknowledging the limitation of using national testing data, we found that children had a lower risk of reinfection compared to adults and that the risk of reinfection in children increased with age. Reinfections were not associated with severe disease in terms of hospitalization or intensive care admission and there were no fatalities within 28 days of the reinfection episode in children. Implications of all the Available EvidenceSARS-CoV-2 reinfections are rare in children, especially younger children, and occurred mainly during the Delta wave in England. Reinfections were not associated with more severe disease or fatal outcomes in children. COVID-19 vaccination will provide further protection against primary infections and reinfections in children.
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Adolescents in the UK were recommended to have their first dose of mRNA vaccine during a period of high community transmission due to the highly transmissible Delta variant, followed by a second dose at an extended interval of 8-12 weeks. We used national SARS-CoV-2 testing, vaccination and hospitalisation data to estimate vaccine effectiveness (VE) using a test-negative case-control design, against PCR-confirmed symptomatic COVID-19 in England. BNT162b2 vaccination in 12-15-year-olds and 16-17-year-olds was associated with lower VE against symptomatic COVID-19 caused by Omicron compared to Delta. Data shows a rapid increase in VE against symptomatic COVID-19 after the second dose for both Delta and Omicron, although this declines to 23% against Omicron after 70+ days. Very high protection was achieved for Delta against hospitalisation after one dose. Our data highlight the importance of the second vaccine dose for protection against symptomatic COVID-19 and raise important questions about the objectives of an adolescent immunisation programme. If prevention of infection is the primary aim, then regular COVID-19 vaccine boosters will be required.
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IntroductionThere are limited data on immune responses after COVID-19 vaccine boosters in individuals receiving primary immunisation with BNT162b2 (Pfizer-BioNTech) or AZD1222 (AstraZeneca). MethodsA prospective, cohort study to assess SARS-CoV-2 antibody responses before and after booster vaccination with BNT162b2 in adults receiving either (i) two BNT162b2 doses <30 days apart (BNT162b2-control), (ii) two BNT162b2 doses [≥]30 days apart (BNT162b2-extended) or (iii) two AZD1222 doses [≥]30 days apart (AZD1222-extended) in London, England. SARS-CoV-2 spike protein antibody geometric mean titres (GMTs) before and 2-4 weeks after booster were compared. ResultsOf 750 participants, 626 provided serum samples for up to 38 weeks after their second vaccine dose. Antibody GMTs peaked at 2-4 weeks after the second dose, before declining by 68% at 36-38 weeks after dose 2 for BNT162b2-control participants, 85% at 24-29 weeks for BNT162b2-extended participants and 78% at 24-29 weeks for AZD1222-extended participants. Antibody GMTs was highest in BNT162b2-extended participants (942 [95%CI, 797-1113]) than AZD1222-extended (183 [124-268]) participants at 24-29 weeks or BNT162b2-control participants at 36-38 weeks (208; 95%CI, 150-289). At 2-4 weeks after booster, GMTs were significantly higher than after primary vaccination in all three groups: 18,104 (95%CI, 13,911-23,560; n=47) in BNT162b2-control (76.3-fold), 13,980 (11,902-16,421; n=118) in BNT162b2-extended (15.9-fold) and 10,799 (8,510-13,704; n=43) in AZD1222-extended (57.2-fold) participants. BNT162b2-control participants (median:262 days) had a longer interval between primary and booster doses than BNT162b2-extended or AZD1222-extended (both median:186 days) participants. ConclusionsWe observed rapid serological responses to boosting with BNT162b2, irrespective of vaccine type or schedule used for primary immunisation, with higher post-booster responses with longer interval between primary immunisation and boosting. Boosters will not only provide additional protection for those at highest risk of severe COVID-19 but also prevent infection and, therefore, interrupt transmission, thereby reducing infections rates in the population. Ongoing surveillance will be important for monitoring the duration of protection after the booster.
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Serological surveillance studies sometimes use presence of anti-nucleocapsid antibody as a marker of natural SARS-CoV-2 infection. We explore seroconversion rates and antibody levels following Alpha and Delta variant infections, and vaccine breakthrough infections. We find lower seroconversion rates particularly following Alpha-variant vaccine breakthrough infections. We re-evaluate assay performance with a mix of past waned infections and recent breakthrough infections, that is relevant to current serological surveillance.
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IntroductionIn January 2021, the UK decided to prioritise the delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval until the second dose up to 12 weeks. MethodsSerological responses were compared after BNT162b2 and AZD1222 vaccination with varying intervals in uninfected and previously-infected adults aged 50-89 years. These findings are evaluated against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. ResultsWe recruited 750 participants aged 50-89 years, including 126 (16.8%) with evidence of previous infection; 421 received BNT162b2 and 329 and AZD1222. For both vaccines, over 95% had seroconverted 35-55 days after dose one, and 100% seroconverted 7+ days after dose 2. Following a 65-84 day interval between two doses, geometric mean titres (GMTs) at 14-34 days were 6-fold higher for BNT162b2 (6703; 95%CI, 5887-7633) than AZD1222 (1093; 806-1483), which in turn were higher than those receiving BNT162b2 19-29 days apart (694; 540 - 893). 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 interval between doses. Higher two-dose VE was observed with >6 week intervals between BNT162b2 doses compared to the authorised 3-week schedule, including [≥]80 year-olds. ConclusionOur findings support the UK approach of prioritising the first dose of COVID-19 vaccines, with evidence of higher protection following extended schedules. Given global vaccine constraints, these results are relevant to policymakers, especially with highly transmissible variants and rising incidence in many countries. FundingPublic Health England
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BackgroundIn England, the rapid spread of the SARS-Cov-2 Alpha (B.1.1.7) variant from November 2020 led to national lockdown, including school closures in January 2021. We assessed SARS-CoV-2 infection, seroprevalence and seroconversion in students and staff when secondary schools reopened in March 2021. MethodsPublic Health England 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). FindingsIn 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 between December 2020 and March 2021. Nucleoprotein antibody seroprevalence was 36.3% (370/1018) in students and 31.9% (245/769) in staff, while spike protein antibody prevalence was 39.5% (402/1018) and 59.8% (459/769), respectively, similar to regional community seroprevalence. Between December 2020 and March 2021 (median 15.9 weeks), 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). InterpretationBy March 2021, a third of secondary school students and staff had serological 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. Further studies are needed to assess the impact of the Delta variant. Research in ContextO_ST_ABSEvidence Before this studyC_ST_ABSThe Alpha variant is 30-70% more transmissible than previously circulating SARS-CoV-2 strains in adults and children. One outbreak investigation in childcare settings estimated similar secondary attack rates with the Alpha variant in children and adults. There are limited data on the impact of the Alpha variant in educational settings. In England, cases in primary and secondary school aged children increased rapidly from late November 2020 and peaked at the end of December 2020, leading to national lockdown including school closures. Added Value of This StudySeroconversion rates in staff and students during December 2020 to March 2021, when the Alpha variant was the primary circulating strain in England, were similar to the period between September 2020 and December 2020 when schools were fully open for in-person teaching. By March 2021, a third of students overall and more than half the students in some regions were seropositive for SARS-CoV-2 antibodies. Among staff, too, around a third had evidence of prior infection on serological testing and a further third had vaccine-induced immunity. Implications of all the Available EvidenceSARS-CoV-2 antibody seroprevalence was high among secondary school students in March 2021 and is likely to be higher following the emergence of an even more transmissible Delta variant in May 2021. Education staff are increasingly being protected by the national COVID-19 immunisation programme. These findings have important implications for countries that are considering vaccination of children to control the pandemic
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Seroepidemiological studies to monitor antibody kinetics are important for assessing the extent and spread of SARS-CoV-2 in a population. Non-invasive sampling methods are advantageous to reduce the need for venepuncture, which may be a barrier to investigations particularly in paediatric populations. Oral Fluids are obtained by gingiva-crevicular sampling from children and adults and are very well accepted. ELISA based on these samples have acceptable sensitivity and specificity compared to conventional serum-based antibody ELISAs and are suitable for population-based surveillance. We describe the development and evaluation of SARS-COV-2 IgG ELISAs using SARS-CoV-2 viral nucleoprotein (NP) and spike (S) proteins in IgG isotype capture format and an indirect receptor-binding-domain (RBD) IgG ELISA, intended for use in children. All three assays were assessed using a panel of 1999 paired serum and oral fluids from children and adults participating in national primary school SARS-CoV-2 surveillance studies during and after the first and second pandemic wave in the UK. The anti NP IgG capture assay was the best candidate, with an overall sensitivity of 75% (95% CI: 71-79%) specificity of 99% (95% CI: 78-99%) when compared with paired serum antibodies measured using a commercial assay SARS-CoV-2 nucleoprotein IgG assay (Abbott, Chicago, IL, USA). Higher sensitivity was observed in children (80%, 95% CI: 71-88%) compared to adults (67%, CI: 60%-74%). Oral fluid assays using spike protein and RBD antigens were also 99% specific and achieved reasonable but lower sensitivity in the target population (78%, 95% CI (68%-86%) and 53%, 95% CI (43%-64%), respectively). Conclusion statementOral Fluid assays based on the detection of SARS-CoV-2 antibodies are a suitable tool for population based seroepidemiology studies in children.
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BackgroundMost individuals with COVID-19 will recover without sequelae, but some will develop long-term multi-system impairments. The definition, duration, prevalence and symptoms associated with long COVID, however, have not been established. MethodsPublic Health England (PHE) initiated longitudinal surveillance of clinical and non-clinical healthcare workers for monthly assessment and blood sampling for SARS-CoV-2 antibodies in March 2020. Eight months after enrolment, participants completed an online questionnaire including 72 symptoms in the preceding month. Symptomatic mild-to-moderate cases with confirmed COVID-19 were compared with asymptomatic, seronegative controls. Multivariable logistic regression was used to identify independent symptoms associated with long COVID. FindingsAll 2,147 participants were contacted and 1,671 (77.8%) completed the questionnaire, including 140 (8.4%) cases and 1,160 controls. At a median of 7.5 (IQR 7.1-7.8) months after infection, 20 cases (14.3%) had ongoing (4/140, 2.9%) or episodic (16/140, 11.4%) symptoms. We identified three clusters of symptoms associated with long COVID, those affecting the sensory (ageusia, anosmia, loss of appetite and blurred vision), neurological (forgetfulness, short-term memory loss and confusion/brain fog) and cardiorespiratory (chest tightness/pain, unusual fatigue, breathlessness after minimal exertion/at rest, palpitations) systems. The sensory cluster had the highest association with being a case (aOR 5.25, 95% CI 3.45-8.01). Dermatological, gynaecological, gastrointestinal or mental health symptoms were not significantly different between cases and controls. InterpretationMost persistent symptoms reported following mild COVID-19 were equally common in cases and controls. While all three clusters identified had a strong association with cases, the sensory cluster had the highest specificity and strength of association, and therefore, most likely to be characteristic of long COVID. FundingPHE. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed using search terms "long covid*" OR "post COVID*" in adults for studies including cohort, case reports, randomised control trials, cross-sectional and systematic reviews published up to 12 March 2020 without any language restrictions. Most reports included a small number of cases. Larger studies included very specific cohorts, including hospitalised cases and self-selected participants with COVID-19. A systematic review identified 15 studies and, using a broad case definition, concluded that 80% (95% CI 65-92) of patients with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%), but no assessment was made of these symptoms in uninfected adults. Added value of this studyIn a prospective, longitudinal cohort of clinical and non-clinical healthcare workers recruited at the start of the pandemic, we found that most self-reported symptoms were as common in 140 adults who developed mild-to-moderate COVID-19 more than 6 months previously compared to 1,160 controls who were asymptomatic and SARS-CoV-2 antibody negative throughout the surveillance period. Compared to controls, we identified three clusters of symptoms affecting the sensory, neurological and cardiorespiratory systems that were more prevalent among cases. Notably, symptoms affecting other organ systems were as prevalent among cases as controls. The high proportion of cases and controls reporting mental health symptoms highlights the toll that the pandemic has had on healthcare workers Implications of all the available evidenceOur findings highlight the importance of including a representative cohort of cases to assess long-term outcomes of COVID-19 as well as appropriate controls to estimate the relative prevalence of self-reported symptoms to accurately define this new syndrome. Our study adds to the evidence-base for long COVID in adults with mild-to-moderate COVID-19 who contribute to the vast majority of 120+ million infections worldwide. This information is not only important for clinicians, patients and the public, but also for policy makers and healthcare providers who are investing heavily in long-term provisions for COVID-19 survivors.
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The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, there is concern that immune responses following natural infection may not be sustained and that this may predispose to recurrent infection. We analysed the magnitude and phenotype of the SARS-CoV-2 cellular immune response in 100 donors at six months following primary infection and related this to the profile of antibody level against spike, nucleoprotein and RBD over the previous six months. T-cell immune responses to SARS-CoV-2 were present by ELISPOT and/or ICS analysis in all donors and are characterised by predominant CD4+ T cell responses with strong IL-2 cytokine expression. Median T-cell responses were 50% higher in donors who had experienced an initial symptomatic infection indicating that the severity of primary infection establishes a setpoint for cellular immunity that lasts for at least 6 months. The T-cell responses to both spike and nucleoprotein/membrane proteins were strongly correlated with the peak antibody level against each protein. The rate of decline in antibody level varied between individuals and higher levels of nucleoprotein-specific T cells were associated with preservation of NP-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 six months following infection although the magnitude of this response is related to the clinical features of primary infection.
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BackgroundThere are limited data on SARS-CoV-2 infection and transmission in educational settings. This information is critical for policy makers and practitioners to ensure the safety of staff, students and the wider community during the COVID-19 pandemic. MethodsPublic Health England initiated enhanced national surveillance following the reopening of educational settings during the summer mini-term on 01 June 2020. COVID-19 related situations in educational settings across England were reviewed daily and followed-up until 31 July 2020. SARS-CoV-2 infection and outbreak rates were calculated for staff and students attending early year settings, primary and secondary schools during June 2020. FindingsThere were 67 single confirmed cases, 4 co-primary cases and 30 COVID-19 outbreaks during June 2020, with a strong correlation between number of outbreaks and regional COVID-19 incidence (0.51 outbreaks for each SARS-CoV-2 infection per 100,000 in the community; p=0.001). Overall, SARS-CoV-2 infections and outbreaks were uncommon across all educational settings. Staff members had an increased risk of SARS-CoV-2 infections compared to students in any educational setting, and the majority of cases linked to outbreaks were in staff. The probable transmission direction for the 30 confirmed outbreaks was: staff-to-staff (n=15), staff-to-student (n=7), student-to-staff (n=6) and student-to-student (n=2). InterpretationSARS-CoV-2 infections and outbreaks were uncommon in educational settings during the first month after the easing of national lockdown in England. The strong correlation with regional SARS-CoV-2 incidence emphasises the importance of controlling community transmission to protect educational settings. Additional interventions should focus on reducing transmission in and among staff members. Fundingnone
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BackgroundWe investigated six London care homes experiencing a COVID-19 outbreak and found very high rates of SARS-CoV-2 infection among residents and staff. Here we report follow-up serological analysis in these care homes five weeks later. MethodsResidents and staff had a convalescent blood sample for SARS-CoV-2 antibody levels and neutralising antibodies by SARS-COV-2 RT-PCR five weeks after the primary COVID-19 outbreak investigation. ResultsOf the 518 residents and staff in the initial investigation, 208/241 (86.3%) surviving residents and 186/254 (73.2%) staff underwent serological testing. Almost all SARS-CoV-2 RT-PCR positive residents and staff were antibody positive five weeks later, whether symptomatic (residents 35/35, 100%; staff, 22/22, 100%) or asymptomatic (residents 32/33, 97.0%; staff 21/22, 95.1%). Symptomatic but SARS-CoV-2 RT-PCR negative residents and staff also had high seropositivity rates (residents 23/27, 85.2%; staff 18/21, 85.7%), as did asymptomatic RT-PCR negative individuals (residents 62/92, 67.3%; staff 95/143, 66.4%). Neutralising antibody was present in 118/132 (89.4%) seropositive individuals and was not associated with age or symptoms. Ten residents (10/108, 9.3%) remained RT-PCR positive, but with lower RT-PCR cycle threshold values; all 7 tested were seropositive. New infections were detected in three residents and one staff member. ConclusionsRT-PCR testing for SARS-CoV-2 significantly underestimates the true extent of an outbreak in institutional settings. Elderly frail residents and younger healthier staff were equally able to mount robust and neutralizing antibody responses to SARS-CoV-2. More than two-thirds of residents and staff members had detectable antibodies against SARS-CoV-2 irrespective of their nasal swab RT-PCR positivity or symptoms status.
