Publications by authors named "Shamez N Ladhani"

144 Publications

Septic Arthritis in adults in Bristol and Bath, United Kingdom, 2006-2018: a 13-year retrospective observational cohort study.

Emerg Microbes Infect 2021 Jun 19:1-26. Epub 2021 Jun 19.

Microbiology Services Bristol, Bristol Royal Infirmary, Bristol, United Kingdom (P. North).

Few studies on adult pneumococcal septic arthritis are sufficiently large enough to assess both epidemiological trends following routine pneumococcal immunization and clinical disease. With major shifts in serotypes causing invasive pneumococcal disease (IPD), we wanted to determine the clinical phenotype of adult septic arthritis caused by . We conducted a retrospective cohort study of pneumococcal infections in Bristol and Bath, UK, 2006-2018. We defined pneumococcal septic arthritis as adults with clinically-confirmed septic arthritis, with pneumococcus isolated from sterile-site culture or urinary antigen test positivity. Clinical records were reviewed for each patient in the cohort.Septic arthritis accounted for 1.7% of all IPD cases. 45 cases of adult pneumococcal septic arthritis occurred, with disease typically affecting older adults and those with underlying comorbidity. 67% patients had another focus of infection during their illness. 66% patients required increased care on discharge and 43% had reduced range of movement. In-hospital case fatality rate was 6.7%. One-year patient mortality was 31%.Currently most cases of adult pneumococcal septic arthritis are due to non-PCV13 serotypes which are associated with more severe disease. PCV13 serotypes had higher prevalence of concomitant pneumococcal infection at another site (36.6% versus 73.7%), increased intensive care or high-dependency unit requirement (0% versus 32.4%), and higher inpatient and 1-year case fatality rate (0% versus 8.8%, and 27.3% versus 32.4% respectively) compared to non-PCV13 serotypes.Pneumococcal septic arthritis remains a small proportion of IPD. However, there is significant associated morbidity and mortality, and pneumococcal septic arthritis requires monitoring in coming years.
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http://dx.doi.org/10.1080/22221751.2021.1945955DOI Listing
June 2021

Causation or confounding: why controls are critical for characterizing long COVID.

Nat Med 2021 Jun 17. Epub 2021 Jun 17.

Immunisation and Countermeasures Division, Public Health England, London, UK.

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http://dx.doi.org/10.1038/s41591-021-01402-wDOI Listing
June 2021

Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.

Lancet Digit Health 2021 06;3(6):e360-e370

Irish Meningitis and Sepsis Reference Laboratory, Children's Health Ireland at Temple Street, Dublin, Ireland; Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.

Background: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic.

Methods: In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed.

Findings: 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27-0·37]) and 82% at 8 weeks (0·18 [0·14-0·23]) following the week in which significant changes in population movements were recorded.

Interpretation: The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide.

Funding: Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).
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http://dx.doi.org/10.1016/S2589-7500(21)00077-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166576PMC
June 2021

Sustained declines in age group-specific rotavirus infection and acute gastroenteritis in vaccinated and unvaccinated individuals during the five years since Rotavirus vaccine introduction in England.

Clin Infect Dis 2021 May 27. Epub 2021 May 27.

Immunisation and Counter-Measures Division, National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5EQ, UK.

Background: The introduction of an oral live-attenuated monovalent rotavirus vaccine (Rotarix ®) into the UK infant immunisation programme in July 2013 was associated with large reductions in laboratory-confirmed rotavirus infections and hospitalisations due to acute gastroenteritis (AGE) within 12 months. Here we report the five-year impact of the programme in England.

Methods: Individuals with laboratory-confirmed rotavirus infections during 2000-2018 and all-cause hospitalisations for AGE during 2007-2018 were identified using national electronic records. Age-specific incidence rate ratios (IRR) and estimated numbers of cases averted in each of the five post-vaccination years were calculated.

Results: There were 206,389 laboratory-confirmed rotavirus infections and 3,657,651 hospitalisations for all-cause AGE. Reductions of 69-83% in laboratory-confirmed rotavirus infections in all age groups and 77-88% in infants aged <1 year in each of the five post-vaccine years are reported, with 11,386-11,633 cases averted annually. All-cause AGE hospitalisations were reduced by 12-35% across all age-groups and by 25-48% in <1 year-olds in the five post-vaccine years, with 24,474-49,278 hospitalisations averted annually. There was strong evidence of indirect (herd) protection, with at least 50% and up to 80% of the non-specific end point of all-cause gastroenteritis (AGE) hospitalisations averted being in unvaccinated age-groups, primarily older adults. Seasonal changes include a possible shift from annual to biennial peaks with lower peak incidence and longer seasons.

Conclusions: There were large and sustained declines in both laboratory-confirmed rotavirus infections and AGE hospitalisations across all age groups in each of the five years since the introduction of the UK rotavirus programme.
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http://dx.doi.org/10.1093/cid/ciab460DOI Listing
May 2021

Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom and Ireland, 2020.

Lancet Reg Health Eur 2021 Apr 22;3:100075. Epub 2021 Mar 22.

Immunisation and Countermeasures Division, Public Health England, London, UK.

Background: Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS), first identified in April 2020, shares features of both Kawasaki disease (KD) and toxic shock syndrome (TSS). The surveillance describes the epidemiology and clinical characteristics of PIMS-TS in the United Kingdom and Ireland.

Methods: Public Health England initiated prospective national surveillance of PIMS-TS through the British Paediatric Surveillance Unit. Paediatricians were contacted monthly to report PIMS-TS, KD and TSS cases electronically and complete a detailed clinical questionnaire. Cases with symptom onset between 01 March and 15 June 2020 were included.

Findings: There were 216 cases with features of PIMS-TS alone, 13 with features of both PIMS-TS and KD, 28 with features of PIMS-TS and TSS and 11 with features of PIMS-TS, KD and TSS, with differences in age, ethnicity, clinical presentation and disease severity between the phenotypic groups. There was a strong geographical and temporal association between SARS-CoV-2 infection rates and PIMS-TS cases. Of those tested, 14.8% (39/264) children had a positive SARS-CoV-2 RT-PCR, and 63.6% (75/118) were positive for SARS-CoV-2 antibodies. In total 44·0% (118/268) required intensive care, which was more common in cases with a TSS phenotype. Three of five children with cardiac arrest had TSS phenotype. Three children (1·1%) died.

Interpretation: The strong association between SARS-CoV-2 infection and PIMS-TS emphasises the importance of maintaining low community infection rates to reduce the risk of this rare but severe complication in children and adolescents. Close follow-up will be important to monitor long-term complications in children with PIMS-TS.

Funding: PHE.
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http://dx.doi.org/10.1016/j.lanepe.2021.100075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132575PMC
April 2021

Seroprevalence of SARS-CoV-2 antibodies in university students: Cross-sectional study, December 2020, England.

J Infect 2021 Apr 29. Epub 2021 Apr 29.

Immunisation and Countermeasures Division, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.

Background: In England, the reopening of universities in September 2020 coincided with a rapid increase in SARS-CoV-2 infection rates in university aged young adults. This study aimed to estimate SARS-CoV-2 antibody prevalence in students attending universities that had experienced a COVID-19 outbreak after reopening for the autumn term in September 2020.

Methods: A cross-sectional serosurvey was conducted during 02-11 December 2020 in students aged ≤ 25 years across five universities in England. Blood samples for SARS-CoV-2 antibody testing were obtained using a self-sampling kit and analysed using the Abbott SARS-CoV-2 N antibody and/or an in-house receptor binding domain (RBD) assay.

Findings: SARS-CoV-2 seroprevalence in 2,905 university students was 17.8% (95%CI, 16.5-19.3), ranging between 7.6%-29.7% across the five universities. Seropositivity was associated with being younger likely to represent first year undergraduates (aOR 3.2, 95% CI 2.0-4.9), living in halls of residence (aOR 2.1, 95% CI 1.7-2.7) and sharing a kitchen with an increasing number of students (shared with 4-7 individuals, aOR 1.43, 95%CI 1.12-1.82; shared with 8 or more individuals, aOR 1.53, 95% CI 1.04-2.24). Seropositivity was 49% in students living in halls of residence that reported high SARS-CoV-2 infection rates (>8%) during the autumn term.

Interpretation: Despite large numbers of cases and outbreaks in universities, less than one in five students (17.8%) overall had SARS-CoV-2 antibodies at the end of the autumn term in England. In university halls of residence affected by a COVID-19 outbreak, however, nearly half the resident students became infected and developed SARS-CoV-2 antibodies.
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http://dx.doi.org/10.1016/j.jinf.2021.04.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081745PMC
April 2021

Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

Microorganisms 2021 Apr 2;9(4). Epub 2021 Apr 2.

National Public Health Organisation, 15123 Athens, Greece.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.
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http://dx.doi.org/10.3390/microorganisms9040742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066045PMC
April 2021

Serotype Distribution of Remaining Pneumococcal Meningitis in the Mature PCV10/13 Period: Findings from the PSERENADE Project.

Microorganisms 2021 Apr 1;9(4). Epub 2021 Apr 1.

Department of Clinical Microbiology, Landspitali-The National University Hospital, Hringbraut, 101 Reykjavik, Iceland.

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites ( = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites ( = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.
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http://dx.doi.org/10.3390/microorganisms9040738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066874PMC
April 2021

Severe Acute Respiratory Syndrome Coronavirus 2 Infections in Primary School Age Children After Partial Reopening of Schools in England.

Pediatr Infect Dis J 2021 06;40(6):e243-e245

From the Division of Immunisation and Countermeasures, Public Health England.

In England, the easing of national lockdown in response to the coronavirus disease 2019 pandemic included the reopening of some primary school years on June 1, 2020. National surveillance did not identify any increase in the year groups attending school. Most children had a severe acute respiratory syndrome coronavirus 2 positive household contact. Hospitalizations for coronavirus disease 2019 were rare, but 2.7% (7/259) had persistent symptoms 1 month later.
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http://dx.doi.org/10.1097/INF.0000000000003120DOI Listing
June 2021

Cross sectional investigation of a COVID-19 outbreak at a London Army barracks: Neutralising antibodies and virus isolation.

Lancet Reg Health Eur 2021 Mar;2:100015

Immunisation and Countermeasures Division, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.

Background: Military personnel in enclosed societies are at increased risk of respiratory infections. We investigated an outbreak of Coronavirus Disease 2019 in a London Army barracks early in the pandemic.

Methods: Army personnel, their families and civilians had nasal and throat swabs for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by reverse transcriptase -polymerase chain reaction (RT-PCR), virus isolation and whole genome sequencing, along with blood samples for SARS-CoV-2 antibodies. All tests were repeated 36 days later.

Findings: During the first visit, 304 (254 Army personnel, 10 family members, 36 civilians, 4 not stated) participated and 24/304 (8%) were SARS-CoV-2 RT-PCR positive. Infectious virus was isolated from 7/24 (29%). Of the 285 who provided a blood sample, 7% (19/285) were antibody positive and 63% (12/19) had neutralising antibodies. Twenty-two (22/34, 64%) individuals with laboratory-confirmed infection were asymptomatic. Nine SARS-CoV-2 RT-PCR positive participants were also antibody positive but those who had neutralising antibodies did not have infectious virus. At the second visit, no new infections were detected, and 13% (25/193) were seropositive, including 52% (13/25) with neutralising antibodies. Risk factors for SARS-CoV-2 antibody positivity included contact with a confirmed case (RR 25.2; 95% CI 14-45), being female (RR 2.5; 95% CI 1.0-6.0) and two-person shared bathroom (RR 2.6; 95% CI 1.1-6.4).

Interpretation: We identified high rates of asymptomatic SARS-CoV-2 infection. Public Health control measures can mitigate spread but virus re-introduction from asymptomatic individuals remains a risk. Most seropositive individuals had neutralising antibodies and infectious virus was not recovered from anyone with neutralising antibodies.

Funding: PHE.
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http://dx.doi.org/10.1016/j.lanepe.2020.100015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834392PMC
March 2021

Changes in Invasive Pneumococcal Disease Caused by Serotype 1 Following Introduction of PCV10 and PCV13: Findings from the PSERENADE Project.

Microorganisms 2021 03 27;9(4). Epub 2021 Mar 27.

National Centre for Immunisation Research and Surveillance and Discipline of Child and Adolescent Health, Children's Hospital Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Westmead, NSW 2145, Australia.

serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04-0.06) for all ages, 0.05 (0.04-0.05) for <5 years of age, 0.08 (0.06-0.09) for 5-17 years, 0.06 (0.05-0.08) for 18-49 years, 0.06 (0.05-0.07) for 50-64 years, and 0.05 (0.04-0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed.
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http://dx.doi.org/10.3390/microorganisms9040696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066231PMC
March 2021

UK guidelines and testing for invasive meningococcal disease.

Lancet Infect Dis 2021 04;21(4):455-456

Immunisation and Countermeasures Division, Public Health England, Colindale, London NW9 5EQ, UK.

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http://dx.doi.org/10.1016/S1473-3099(21)00092-XDOI Listing
April 2021

Robust antibody responses in 70-80-year-olds 3 weeks after the first or second doses of Pfizer/BioNTech COVID-19 vaccine, United Kingdom, January to February 2021.

Euro Surveill 2021 03;26(12)

Immunisation and Countermeasures Division, National Infection Service, Public Health England, London, United Kingdom.

Sera were collected from 185 adults aged ≥ 70 years in London to evaluate the immune response to COVID-19 vaccines. A single dose of Pfizer/BioNtech vaccine resulted in > 94% seropositivity after 3 weeks in naïve individuals using the Roche Spike antibody assay, while two doses produced very high spike antibody levels, significantly higher than convalescent sera from mild-to-moderate PCR-confirmed adult cases. Our findings support the United Kingdom's approach of prioritising the first dose and delaying the second dose of COVID-19 vaccine.
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http://dx.doi.org/10.2807/1560-7917.ES.2021.26.12.2100329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995559PMC
March 2021

Serological surveillance of SARS-CoV-2: Six-month trends and antibody response in a cohort of public health workers.

J Infect 2021 05 22;82(5):162-169. Epub 2021 Mar 22.

Immunisation and Countermeasures Division, PHE Colindale, National Infection Service, 61 Colindale Avenue, London NW9 5EQ, UK; Paediatric Infectious Diseases Research Group (PIDRG), St. Georges University of London (SGUL), London, UK. Electronic address:

Background: Antibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England.

Methods: Clinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays. In positive individuals, antibody responses and long-term trends were modelled using mixed effects regression.

Findings: In total, 2246 individuals attended 12,247 visits and 264 were seropositive in ≥ 2 assays. Most seroconversions occurred between March and April 2020. The assays showed > 85% agreement for ever-positivity, although this changed markedly over time. Antibodies were detected earlier with Abbott (N) but declined rapidly thereafter. With the EuroImmun (S) and receptor-binding domain (RBD) assays, responses increased for 4 weeks then fell until week 12-16 before stabilising. For Roche (N), responses increased until 8 weeks, stabilised, then declined, but most remained above the positive threshold. For Roche (S), responses continued to climb over the full 24 weeks, with no sero-reversions. Predicted proportions sero-reverting after 52 weeks were 100% for Abbott, 59% (95% credible interval 50-68%) Euroimmun, 41% (30-52%) RBD, 10% (8-14%) Roche (N) < 2% Roche (S).

Interpretation: Trends in SARS-CoV-2 antibodies following infection are highly dependent on the assay used. Ongoing serosurveillance using multiple assays is critical for monitoring the course and long-term progression of SARS-CoV-2 antibodies.
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http://dx.doi.org/10.1016/j.jinf.2021.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982645PMC
May 2021

SARS-CoV-2 infection and transmission in primary schools in England in June-December, 2020 (sKIDs): an active, prospective surveillance study.

Lancet Child Adolesc Health 2021 06 17;5(6):417-427. Epub 2021 Mar 17.

National Infection Service, Public Health England, London, UK.

Background: Little is known about the risk of SARS-CoV-2 infection and transmission in educational settings. Public Health England initiated a study, COVID-19 Surveillance in School KIDs (sKIDs), in primary schools when they partially reopened from June 1, 2020, after the first national lockdown in England to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, seroprevalence, and seroconversion in staff and students.

Methods: sKIDs, an active, prospective, surveillance study, included two groups: the weekly swabbing group and the blood sampling group. The swabbing group underwent weekly nasal swabs for at least 4 weeks after partial school reopening during the summer half-term (June to mid-July, 2020). The blood sampling group additionally underwent blood sampling for serum SARS-CoV-2 antibodies to measure previous infection at the beginning (June 1-19, 2020) and end (July 3-23, 2020) of the summer half-term, and, after full reopening in September, 2020, and at the end of the autumn term (Nov 23-Dec 18, 2020). We tested for predictors of SARS-CoV-2 antibody positivity using logistic regression. We calculated antibody seroconversion rates for participants who were seronegative in the first round and were tested in at least two rounds.

Findings: During the summer half-term, 11 966 participants (6727 students, 4628 staff, and 611 with unknown staff or student status) in 131 schools had 40 501 swabs taken. Weekly SARS-CoV-2 infection rates were 4·1 (one of 24 463; 95% CI 0·1-21·8) per 100 000 students and 12·5 (two of 16 038; 1·5-45·0) per 100 000 staff. At recruitment, in 45 schools, 91 (11·2%; 95% CI 7·9-15·1) of 816 students and 209 (15·1%; 11·9-18·9) of 1381 staff members were positive for SARS-CoV-2 antibodies, similar to local community seroprevalence. Seropositivity was not associated with school attendance during lockdown (p=0·13 for students and p=0·20 for staff) or staff contact with students (p=0·37). At the end of the summer half-term, 603 (73·9%) of 816 students and 1015 (73·5%) of 1381 staff members were still participating in the surveillance, and five (four students, one staff member) seroconverted. By December, 2020, 55 (5·1%; 95% CI 3·8-6·5) of 1085 participants who were seronegative at recruitment (in June, 2020) had seroconverted, including 19 (5·6%; 3·4-8·6) of 340 students and 36 (4·8%; 3·4-6·6) of 745 staff members (p=0·60).

Interpretation: In England, SARS-CoV-2 infection rates were low in primary schools following their partial and full reopening in June and September, 2020.

Funding: UK Department of Health and Social Care.
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http://dx.doi.org/10.1016/S2352-4642(21)00061-4DOI Listing
June 2021

Invasive pneumococcal disease due to 22F and 33F in England: A tail of two serotypes.

Vaccine 2021 04 11;39(14):1997-2004. Epub 2021 Mar 11.

Immunisation and Countermeasures Division, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK; Paediatric Infectious Diseases Research Group, St. George's University of London, Cranmer Terrace, London SW17 0RE, UK. Electronic address:

Background: A 15-valent pneumococcal conjugate vaccine (PCV15) aims to protect against serotype 22F and 33F in addition to the serotypes within the 13-valent PCV (PCV13) which was introduced to the UK childhood immunisation programme in April 2010. Little is known about the specific epidemiology, clinical features or outcomes of invasive pneumococcal disease (IPD) due to these two serotypes.

Methods: Public Health England (PHE) conducts enhanced IPD surveillance in England. Hospital laboratories routinely submit invasive pneumococcal isolates to PHE for serotyping and enhanced clinical information is collected through questionnaires sent to general practitioners. IPD due to serotypes 22F and 33F diagnosed during 2014/15-2018/19 were compared with IPD due to PCV13 serotypes and remaining serotypes.

Results: In total, 25,415 isolates (93.4%) were serotyped and questionnaires were completed for 22,097 (86.9%) cases. Serotype 22F was responsible for 1,788 (7.0%) and serotype 33F for 893 (3.5%) cases compared to 19.9% (n = 5,047) for PCV13 and 69.6% (n = 17,687) for the remaining serotypes. IPD incidence increased for both serotypes since 2005/06, especially in older adults, but plateaued after PCV13 introduction. Comorbidity prevalence was 68.7% (n = 1,037) for serotype 22F and 67.2% (n = 505) for serotype 33F, with invasive pneumonia being the most common clinical presentation 1,067/1,482; 72.0%, and 514/755; 68.1%, respectively. There were 3,617 deaths within 30 days of disease onset, including 236 (CFR, 15.4%) among 22F, 128 (CFR, 16.5%) among 33F and 21.3% (925/4,350) among PCV13-type IPD cases. When compared with PCV13-type IPD, serotype 22F (aOR 0.58, 95%CI 0.49-0.68, p < 0.001) and 33F (aOR 0.73, 95%CI 0.59-0.91, p = 0.004) were independently associated with lower odds of death. The major circulating sequence types (STs) in 22F (ST 433, ST698) and 33F (ST717, ST100, ST673) were not associated with an increased risk of death compared to the other STs.

Conclusions: Serotype 22F and 33F-type IPD are associated with a lower risk of death compared to PCV13-type, with those presenting with septicaemia more likely to have a fatal outcome compared to pneumonia. PCV15 has the potential to prevent up to an additional 10% of IPD cases in England.
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http://dx.doi.org/10.1016/j.vaccine.2021.02.026DOI Listing
April 2021

SARS-CoV-2 infections in children following the full re-opening of schools and the impact of national lockdown: Prospective, national observational cohort surveillance, July-December 2020, England.

J Infect 2021 04 25;82(4):67-74. Epub 2021 Feb 25.

Immunisation and Countermeasures Division, National Infection Service, Public Health England, London NW9 5EQ, UK; Paediatric Infectious Diseases Research Group (PIDRG), St George's University of London, Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK. Electronic address:

Introduction: The reopening of schools during the COVID-19 pandemic has raised concern for the safety of staff and students, their families and the wider community. We monitored SARS-CoV-2 infection rates in school-aged children and compared them with adult infection rates before and after schools reopened in England.

Methods: Public Health England receives daily electronic reports of all SARS-CoV-2 tests nationally. SARS-CoV-2 infection rates by school year from July to December 2020 were analysed, including the effect of a national month-long lockdown whilst keeping schools open in November 2020 RESULTS: SARS-CoV-2 infections rates were low during early summer but started increasing in mid-August, initially in young adults followed by secondary and then primary school-aged children prior to schools reopening in September 2020. Cases in school-aged children lagged behind and followed adult trends after schools reopened, with a strong age gradient in weekly infection rates. There was a strong (P<0.001) correlation in regional infection rates between adults and secondary (R=0.96-0.98), primary (R=0.93-0.94) and preschool-aged (R=0.62-0.85) children. The November lockdown was associated with declines in adult infection rates, followed a week later, by declines in student cases. From 23 November 2020, cases in adults and children increased rapidly following the emergence of a more transmissible novel variant of concern (VOC-202,012/01; B.1.1.7).

Conclusions: In school-aged children, SARS-CoV-2 infections followed the same trajectory as adult cases and only declined after national lockdown was implemented whilst keeping schools open. Maintaining low community infection rates is critical for keeping schools open during the pandemic.
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http://dx.doi.org/10.1016/j.jinf.2021.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904496PMC
April 2021

Similar impact and replacement disease after pneumococcal conjugate vaccine introduction in hospitalised children with invasive pneumococcal disease in Europe and North America.

Vaccine 2021 03 18;39(11):1551-1555. Epub 2021 Feb 18.

Department of Infectious Disease Epidemiology, Faculty of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London, UK.

High incidence of childhood invasive pneumococcal disease (IPD) in the US declined steeply after 7-valent pneumococcal conjugate vaccine (PCV7) introduction, outweighing reductions observed elsewhere. We re-analysed aggregate published data and compared pre- and post-PCV IPD-incidence in different countries to explore PCV impact on hospitalised and outpatient IPD separately. The proportion of hospitalised IPD cases was consistently high (>80%) in England&Wales, Finland, the Netherlands, and Quebec/Canada, but only 32% in the US before PCV introduction, increasing to 69% during the PCV era. In the US, a higher reduction in outpatient IPD incidence (94% in 2015 versus 1998-99) was observed compared to hospitalised IPD (79%); a 51% reduction in the non-PCV13-type IPD incidence among outpatient cases was estimated compared to a >2-fold increase for hospitalised cases. After stratification by hospitalization status, PCV programmes resulted in similar impact and serotype replacement in hospitalised IPD in US when compared to other countries.
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http://dx.doi.org/10.1016/j.vaccine.2021.01.070DOI Listing
March 2021

Antibodies to SARS-CoV-2 protect against re-infection during outbreaks in care homes, September and October 2020.

Euro Surveill 2021 02;26(5)

National Infection Service Public Health England, London, United Kingdom.

Two London care homes experienced a second COVID-19 outbreak, with 29/209 (13.9%) SARS-CoV-2 RT-PCR-positive cases (16/103 residents, 13/106 staff). In those with prior SARS-CoV-2 exposure, 1/88 (1.1%) individuals (antibody positive: 87; RT-PCR-positive: 1) became PCR-positive compared with 22/73 (30.1%) with confirmed seronegative status. After four months protection offered by prior infection against re-infection was 96.2% (95% confidence interval (CI): 72.7-99.5%) using risk ratios from comparison of proportions and 96.1% (95% CI: 78.8-99.3%) using a penalised logistic regression model.
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http://dx.doi.org/10.2807/1560-7917.ES.2021.26.5.2100092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863231PMC
February 2021

Meningococcal carriage in periods of high and low invasive meningococcal disease incidence in the UK: comparison of UKMenCar1-4 cross-sectional survey results.

Lancet Infect Dis 2021 05 19;21(5):677-687. Epub 2021 Jan 19.

Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the National Institute for Health Research Oxford Biomedical Research Centre, Oxford, UK.

Background: The incidence of invasive meningococcal disease in the UK decreased by approximately four times from 1999 to 2014, with reductions in serogroup C and serogroup B disease. Lower serogroup C invasive meningococcal disease incidence was attributable to implementation of the meningococcal serogroup C conjugate vaccine in 1999, through direct and indirect protection, but no vaccine was implemented against serogroup B disease. UK Meningococcal Carriage surveys 1-3 (UKMenCar1-3), conducted in 1999, 2000, and 2001, were essential for understanding the impact of vaccination. To investigate the decline in invasive meningococcal disease incidence, we did a large oropharyngeal carriage survey in 2014-15, immediately before the changes to meningococcal vaccines in the UK national immunisation schedule.

Methods: UKMenCar4 was a cross-sectional survey in adolescents aged 15-19 years who were enrolled from schools and colleges geographically local to one of 11 UK sampling centres between Sept 1, 2014, and March 30, 2015. Participants provided an oropharyngeal swab sample and completed a questionnaire on risk factors for carriage, including social behaviours. Samples were cultured for putative Neisseria spp, which were characterised with serogrouping and whole-genome sequencing. Data from this study were compared with the results from the UKMenCar1-3 surveys (1999-2001).

Findings: From the 19 641 participants (11 332 female, 8242 male, 67 not stated) in UKMenCar4 with culturable swabs and completed risk-factor questionnaires, 1420 meningococci were isolated, with a carriage prevalence of 7·23% (95% CI 6·88-7·60). Carriage prevalence was substantially lower in UKMenCar4 than in the previous surveys: carriage prevalence was 16·6% (95% CI 15·89-17·22; 2306/13 901) in UKMenCar1 (1999), 17·6% (17·05-18·22; 2873/16 295) in UKMenCar2 (2000), and 18·7% (18·12-19·27; 3283/17 569) in UKMenCar3 (2001). Carriage prevalence was lower for all serogroups in UKMenCar4 than in UKMenCar1-3, except for serogroup Y, which was unchanged. The prevalence of carriage-promoting social behaviours decreased from 1999 to 2014-15, with individuals reporting regular cigarette smoking decreasing from 2932 (21·5%) of 13 650 to 2202 (11·2%) of 19 641, kissing in the past week from 6127 (44·8%) of 13 679 to 7320 (37·3%) of 19 641, and attendance at pubs and nightclubs in the past week from 8436 (62·1%) of 13 594 to 7662 (39·0%) of 19 641 (all p<0·0001).

Interpretation: We show that meningococcal carriage prevalence in adolescents sampled nationally during a low incidence period (2014-15) was less than half of that in an equivalent population during a high incidence period (1999-2001). Disease and carriage caused by serogroup C was well controlled by ongoing vaccination. The prevalence of behaviours associated with carriage declined, suggesting that public health policies aimed at influencing behaviour might have further reduced disease.

Funding: Wellcome Trust, UK Department of Health, and National Institute for Health Research.
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http://dx.doi.org/10.1016/S1473-3099(20)30842-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064914PMC
May 2021

Seroprevalence of SARS-CoV-2 antibodies in children of United Kingdom healthcare workers: a prospective multicentre cohort study protocol.

BMJ Open 2020 11 19;10(11):e041661. Epub 2020 Nov 19.

Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast- School of Medicine, Dentistry and Biomedical Sciences, Belfast, UK

Background: A novel coronavirus SARS-CoV-2 has been responsible for a worldwide pandemic. Children typically have very mild, or no, symptoms of infection. This makes estimations of seroprevalence in children difficult. Research is therefore required to determine the seroprevalence of SARS-CoV-2 antibodies in children. The primary objective of this study is to report the seroprevalence of SARS-CoV-2 IgM and/or IgG antibodies in healthy children at baseline, 2 months and 6 months. This is the only longitudinal UK study of seroprevalence in an exclusively paediatric population. Determining the changing seroprevalence is of vital public health importance and can help inform decisions around the lifting of paediatric specific social distancing measures such as school closures and the cancellation of routine paediatric hospital services.

Methods And Analysis: 1000 healthy children of healthcare workers aged between 2 and 15 years will be recruited from five UK sites (Belfast, Cardiff, Glasgow, London and Manchester). The children will undergo phlebotomy at baseline, 2 months and 6 months to measure IgM and/or IgG positivity to SARS-CoV-2. A sample size of 675 patients is required to detect a 5% change in seroprevalence at each time point assuming an alpha of 0.05 and a beta of 0.2. Adjusted probabilities for the presence of IgG and/or IgM antibodies and of SARS-CoV-2 infection will be reported using logistic regression models where appropriate.

Ethics And Dissemination: Ethical approval was obtained from the London - Chelsea Research Ethics Committee (REC Reference-20/HRA/1731) and the Belfast Health & Social Care Trust Research Governance (Reference 19147TW-SW). Results of this study will be made available as preprints and submitted for publication in peer-reviewed journals.

Trial Registration Number: NCT0434740; Results.
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http://dx.doi.org/10.1136/bmjopen-2020-041661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678379PMC
November 2020

Should children be vaccinated against COVID-19 now?

Arch Dis Child 2021 Jan 5. Epub 2021 Jan 5.

Immunisation and Countermeasures Division, Public Health England, Colindale, London, UK

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http://dx.doi.org/10.1136/archdischild-2020-321225DOI Listing
January 2021

Killing 2 Cocci With 1 Vaccine: Unleashing the Full Potential of an Adolescent Meningococcal B Immunization Program.

Clin Infect Dis 2020 Dec 19. Epub 2020 Dec 19.

Immunisation and Countermeasures Division, Public Health England, London, United Kingdom.

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http://dx.doi.org/10.1093/cid/ciaa1644DOI Listing
December 2020

SARS-CoV-2 infection and transmission in educational settings: a prospective, cross-sectional analysis of infection clusters and outbreaks in England.

Lancet Infect Dis 2021 03 8;21(3):344-353. Epub 2020 Dec 8.

Immunisation and Countermeasures Division, Public Health England, London, UK; Paediatric Infectious Diseases Research Group, St George's University of London, London, UK.

Background: Understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission in educational settings is crucial for ensuring the safety of staff and children during the COVID-19 pandemic. We estimated the rate of SARS-CoV-2 infection and outbreaks among staff and students in educational settings during the summer half-term (June-July, 2020) in England.

Methods: In this prospective, cross-sectional analysis, Public Health England initiated enhanced national surveillance in educational settings in England that had reopened after the first national lockdown, from June 1 to July 17, 2020. Educational settings were categorised as early years settings (<5-year-olds), primary schools (5-11-year-olds; only years 1 and 6 allowed to return), secondary schools (11-18-year-olds; only years 10 and 12), or mixed-age settings (spanning a combination of the above). Further education colleges were excluded. Data were recorded in HPZone, an online national database for events that require public health management. RT-PCR-confirmed SARS-CoV-2 event rates and case rates were calculated for staff and students, and direction of transmission was inferred on the basis of symptom onset and testing dates. Events were classified as single cases, coprimary cases (at least two confirmed cases within 48 h, typically within the same household), and outbreaks (at least two epidemiologically linked cases, with sequential cases diagnosed within 14 days in the same educational setting). All events were followed up for 28 days after educational settings closed for the summer holidays. Negative binomial regression was used to correlate educational setting events with regional population, population density, and community incidence.

Findings: A median of 38 000 early years settings (IQR 35 500-41 500), 15 600 primary schools (13 450-17 300), and 4000 secondary schools (3700-4200) were open each day, with a median daily attendance of 928 000 students (630 000-1 230 000) overall. There were 113 single cases of SARS-CoV-2 infection, nine coprimary cases, and 55 outbreaks. The risk of an outbreak increased by 72% (95% CI 28-130) for every five cases per 100 000 population increase in community incidence (p<0·0001). Staff had higher incidence than students (27 cases [95% CI 23-32] per 100 000 per day among staff compared with 18 cases [14-24] in early years students, 6·0 cases [4·3-8·2] in primary schools students, and 6·8 cases [2·7-14] in secondary school students]), and most cases linked to outbreaks were in staff members (154 [73%] staff vs 56 [27%] children of 210 total cases). Probable direction of transmission was staff to staff in 26 outbreaks, staff to student in eight outbreaks, student to staff in 16 outbreaks, and student to student in five outbreaks. The median number of secondary cases in outbreaks was one (IQR 1-2) for student index cases and one (1-5) for staff index cases.

Interpretation: SARS-CoV-2 infections and outbreaks were uncommon in educational settings during the summer half-term in England. The strong association with regional COVID-19 incidence emphasises the importance of controlling community transmission to protect educational settings. Interventions should focus on reducing transmission in and among staff.

Funding: Public Health England.
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http://dx.doi.org/10.1016/S1473-3099(20)30882-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833602PMC
March 2021

Stillbirths During the COVID-19 Pandemic in England, April-June 2020.

JAMA 2021 01;325(1):86-87

Public Health England, Immunisation and Countermeasures Division, London, England.

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http://dx.doi.org/10.1001/jama.2020.21369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786243PMC
January 2021

Secondary attack rate and family clustering of SARS-CoV-2 infection in children of healthcare workers with confirmed COVID-19.

Clin Infect Dis 2020 Nov 17. Epub 2020 Nov 17.

Thomas Waterfield, Centre For Experimental Medicine, Wellcome Wolfson Institute of Experimental Medicine, Queen's University Belfast, Belfast, UK.

We measured serum SARS-CoV-2 antibodies in 215 children of healthcare workers to estimate secondary attack rates (SAR). Twenty-one families had a parent with confirmed COVID-19. There was strong evidence of family clustering (P<0.001): 20/21 (95.2%) children were seropositive in 9 families and none of 23 children in 12 other families.
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http://dx.doi.org/10.1093/cid/ciaa1737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717200PMC
November 2020

Impact of the Coronavirus Disease 2019 (COVID-19) Pandemic on Invasive Pneumococcal Disease and Risk of Pneumococcal Coinfection With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Prospective National Cohort Study, England.

Clin Infect Dis 2021 03;72(5):e65-e75

Immunisation and Countermeasures Division, Public Health England, London, United Kingdom.

Background: Streptococcus pneumoniae coinfection with influenza results in synergistic lethality, but there are limited data on pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: Public Health England conducts invasive pneumococcal disease (IPD) and SARS-CoV-2 surveillance in England. IPD trends during 2000/2001-2019/2020 epidemiological years were analyzed and cases during February-June 2020 linked with laboratory-confirmed SARS-CoV-2 infections. Multivariable logistic regression was used to assess risk factors for death.

Results: IPD incidence in 2019/2020 (7.6/100 000; n = 3964) was 30% (IRR, .70; 95% CI, .18-2.67) lower compared with 2018/2019 (10.9/100 000; n = 5666), with large reductions observed across all age groups during March-June 2020. There were 160 886 SARS-CoV-2 and 1137 IPD cases during February-June 2020, including 40 IPD/coronavirus disease 2019 (COVID-19) co-infections (.025% [95% CI, .018-.034] of SARS-CoV-2 infections; 3.5% [2.5-4.8] of IPD cases), 21 with COVID-19 diagnosed 3-27 days after IPD, and 27 who developed COVID-19 ≥28 days after IPD. Case-fatality rates (CFRs) were 62.5 (25/40), 47.6% (10/21), and 33.3% (9/27), respectively (P < .001). In addition to an independent association with increasing age and serotype group, CFR was 7.8-fold (95% CI, 3.8-15.8) higher in those with IPD/COVID-19 coinfection and 3.9-fold (95% CI, 1.4-10.7) higher in patients who developed COVID-19 3-27 days after IPD compared with patients with IPD only.

Conclusions: Large declines in IPD were observed following COVID-19 lockdown. IPD/COVID-19 coinfections were rare but associated with high CFR, mainly in older adults. The rarity, age and serotype distribution of IPD/COVID-19 coinfections do not support wider extension of pneumococcal vaccination.
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http://dx.doi.org/10.1093/cid/ciaa1728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717180PMC
March 2021

High prevalence of SARS-CoV-2 antibodies in care homes affected by COVID-19: Prospective cohort study, England.

EClinicalMedicine 2020 Nov 6;28:100597. Epub 2020 Nov 6.

Virus Reference Department, Public Health England, London, UK.

Background: We investigated six London care homes experiencing a COVID-19 outbreak and found high rates of SARS-CoV-2 infection among residents and staff. Here we report follow-up investigations including antibody testing in the same care homes five weeks later.

Methods: Residents and staff in the initial investigation had a repeat nasal swab for SARS-CoV-2 RT-PCR and a blood test for SARS CoV-2 antibodies using ELISA based on SARS-CoV-2 native viral antigens derived from infected cells and virus neutralisation.

Findings: Of the 518 residents and staff in the initial investigation, 186/241 (77.2%) surviving residents and 208/254 (81.9%) staff underwent serological testing. Almost all SARS-CoV-2 RT-PCR positive residents and staff were seropositive five weeks later, whether symptomatic (residents 35/35, 100%; staff, 22/22, 100%) or asymptomatic (residents 32/33, 97.0%; staff 21/22, 95.5%). 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 61/91, 67.0%; staff 95/143, 66.4%). Neutralising antibody was detected in 118/132 (89.4%) seropositive individuals and was not associated with age or symptoms. Ten residents (10/79 re-tested, 12.7%) remained RT-PCR positive but with higher RT-PCR cycle threshold values; 7/10 had serological testing and all were seropositive. New infections were detected in three residents and one staff.

Interpretation: RT-PCR provides a point prevalence of SARS-CoV-2 infection but significantly underestimates total exposure in outbreak settings. In care homes experiencing large COVID-19 outbreaks, most residents and staff had neutralising SARS-CoV-2 antibodies, which was not associated with age or symptoms.

Funding: PHE.
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http://dx.doi.org/10.1016/j.eclinm.2020.100597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644437PMC
November 2020