Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have been used since December 2020 in the United Kingdom. Real-world data have shown the vaccines to be highly effective against Covid-19 and related severe disease and death. Vaccine effectiveness may wane over time since the receipt of the second dose of the ChAdOx1-S (ChAdOx1 nCoV-19) and BNT162b2 vaccines. METHODS: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic Covid-19 and related hospitalization and death in England. Effectiveness of the ChAdOx1-S and BNT162b2 vaccines was assessed according to participant age and status with regard to coexisting conditions and over time since receipt of the second vaccine dose to investigate waning of effectiveness separately for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants. RESULTS: Vaccine effectiveness against symptomatic Covid-19 with the delta variant peaked in the early weeks after receipt of the second dose and then decreased by 20 weeks to 44.3% (95% confidence interval [CI], 43.2 to 45.4) with the ChAdOx1-S vaccine and to 66.3% (95% CI, 65.7 to 66.9) with the BNT162b2 vaccine. Waning of vaccine effectiveness was greater in persons 65 years of age or older than in those 40 to 64 years of age. At 20 weeks or more after vaccination, vaccine effectiveness decreased less against both hospitalization, to 80.0% (95% CI, 76.8 to 82.7) with the ChAdOx1-S vaccine and 91.7% (95% CI, 90.2 to 93.0) with the BNT162b2 vaccine, and death, to 84.8% (95% CI, 76.2 to 90.3) and 91.9% (95% CI, 88.5 to 94.3), respectively. Greater waning in vaccine effectiveness against hospitalization was observed in persons 65 years of age or older in a clinically extremely vulnerable group and in persons 40 to 64 years of age with underlying medical conditions than in healthy adults. CONCLUSIONS: We observed limited waning in vaccine effectiveness against Covid-19-related hospitalization and death at 20 weeks or more after vaccination with two doses of the ChAdOx1-S or BNT162b2 vaccine. Waning was greater in older adults and in those in a clinical risk group.

Effects of BNT162b2 Messenger RNA Vaccine and ChAdOx1 Adenovirus Vector Vaccine on Deaths From COVID-19 in Adults Aged ≥70 Years.

We estimated the risk of death from coronavirus disease 2019 in vaccinated compared with unvaccinated patients. The risk of death was reduced 44% after 1 dose of the Pfizer-BioNTech BNT162b2 vaccine, 55% after 1 dose of the Oxford-Astrazeneca ChAdOx1 vaccine, and 69% after 2 doses of the BNT162b2 vaccine. This is above the protection provided against infection.

Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant.

BACKGROUND: The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear. METHODS: We used a test-negative case-control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike (S) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients' vaccination status. RESULTS: Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. CONCLUSIONS: Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.).

Optimization of Timing of Maternal Pertussis Immunization From 6 Years of Postimplementation Surveillance Data in England.

BACKGROUND: England's third-trimester maternal pertussis vaccination, introduced in October 2012, was extended to the second trimester in 2016. Maternal vaccination provides high protection against infant disease, but routine second-trimester vaccination has not previously been assessed. METHODS: National laboratory-confirmed pertussis case surveillance determined vaccination history, maternal vaccination history and hospitalization. Pertussis hospital admissions between 2012 and 2019 were extracted from the Hospital Episode Statistics data set. Vaccine effectiveness (VE) was calculated for pertussis case patients born between October 2012 and September 2018 using the screening method and matching with a nationally representative data set. RESULTS: Higher coverage was observed after earlier maternal vaccination with approximately 40% of pregnant women vaccinated ≥13 weeks before delivery. Cases and hospitalizations stabilized at low levels in younger infants but remained elevated in older infants, children, and adults. No deaths occurred in infants with vaccinated mothers after 2016. Of 1162 laboratory-confirmed pertussis cases in the study, 599 (52%) were in infants aged <93 days: 463 (77%) with unvaccinated and 136 (23%) with vaccinated mothers. The VE was equivalent in infants with mothers vaccinated at different gestational periods except in those with mothers vaccinated between 7 days before and 41 days after delivery. Children whose mothers were unvaccinated but with vaccination in a previous pregnancy had a VE against disease of 44% (95% confidence interval, 19%-75%). There was no increased disease risk after primary vaccination in children with mothers vaccinated at least 7 days before delivery. CONCLUSIONS: National policy recommending vaccination in the second trimester increased earlier maternal vaccine uptake with sustained high VE and impact against early infant disease.

Making the invisible visible: using national surveillance data to identify people experiencing homelessness in England with COVID-19.

Persons experiencing homelessness (PEH) or rough sleeping are a vulnerable population, likely to be disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic. The impact of COVID-19 infection on this population is yet to be fully described in England. We present a novel method to identify COVID-19 cases in this population and describe its findings. A phenotype was developed and validated to identify PEH or rough sleeping in a national surveillance system. Confirmed COVID-19 cases in England from March 2020 to March 2022 were address-matched to known homelessness accommodations and shelters. Further cases were identified using address-based indicators, such as NHS pseudo postcodes. In total, 1835 cases were identified by the phenotype. Most were <39 years of age (66.8%) and male (62.8%). The proportion of cases was highest in London (29.8%). The proportion of cases of a minority ethnic background and deaths were disproportionality greater in this population, compared to all COVID-19 cases in England. This methodology provides an approach to track the impact of COVID-19 on a subset of this population and will be relevant to policy making. Future surveillance systems and studies may benefit from this approach to further investigate the impact of COVID-19 and other diseases on select populations.

Comparative transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants and the impact of vaccination: national cohort study, England.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) rapidly replaced Delta (B.1.617.2) to become dominant in England. Our study assessed differences in transmission between Omicron and Delta using two independent data sources and methods. Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for named contacts were calculated in household and non-household settings using contact tracing data, while household clustering was identified using national surveillance data. Logistic regression models were applied to control for factors associated with transmission for both methods. For contact tracing data, higher secondary attack rates for Omicron vs. Delta were identified in households (15.0% vs. 10.8%) and non-households (8.2% vs. 3.7%). For both variants, in household settings, onward transmission was reduced from cases and named contacts who had three doses of vaccine compared to two, but this effect was less pronounced for Omicron (adjusted risk ratio, aRR 0.78 and 0.88) than Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed only in contacts who had three doses vs. two doses for both Delta (aRR 0.51) and Omicron (aRR 0.76). For national surveillance data, the risk of household clustering, was increased 3.5-fold for Omicron compared to Delta (aRR 3.54 (3.29-3.81)). Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.

High attack rate in a large care home outbreak of SARS-CoV-2 BA.2.86, East of England, August 2023.

We investigated an outbreak of SARS-CoV-2 variant BA.2.86 in an East of England care home. We identified 45 infections (33 residents, 12 staff), among 38 residents and 66 staff. Twenty-nine of 43 PCR swabs were sequenced, all of which were variant BA.2.86. The attack rate among residents was 87%, 19 were symptomatic, and one was hospitalised. Twenty-four days after the outbreak started, no cases were still unwell. Among the 33 resident cases, 29 had been vaccinated 4 months earlier.

Long-Term Health-Related Quality of Life in Non-Hospitalized Coronavirus Disease 2019 (COVID-19) Cases With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in England: Longitudinal Analysis and Cross-Sectional Comparison With Controls.

BACKGROUND: We aimed to quantify the unknown losses in health-related quality of life of coronavirus disease 2019 (COVID-19) cases using quality-adjusted lifedays (QALDs) and the recommended EQ-5D instrument in England. METHODS: Prospective cohort study of nonhospitalized, polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2-positive (SARS-CoV-2-positive) cases aged 12-85 years and followed up for 6 months from 1 December 2020, with cross-sectional comparison to SARS-CoV-2-negative controls. Main outcomes were QALD losses; physical symptoms; and COVID-19-related private expenditures. We analyzed results using multivariable regressions with post hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. RESULTS: Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on nonprescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 13.7 (95% confidence interval [CI]: 9.7, 17.7) QALDs, whereas those reporting symptoms at month 6 lost 32.9 (95% CI: 24.5, 37.6) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 18% of the total COVID-19-related disease burden in the England. CONCLUSIONS: One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms.

Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data.

BACKGROUND: In 2020, the SARS-CoV-2 (COVID-19) pandemic and lockdown control measures threatened to disrupt routine childhood immunisation programmes with early reports suggesting uptake would fall. In response, public health bodies in Scotland and England collected national data for childhood immunisations on a weekly or monthly basis to allow for rapid analysis of trends. The aim of this study was to use these data to assess the impact of different phases of the pandemic on infant and preschool immunisation uptake rates. METHODS AND FINDINGS: We conducted an observational study using routinely collected data for the year prior to the pandemic (2019) and immediately before (22 January to March 2020), during (23 March to 26 July), and after (27 July to 4 October) the first UK "lockdown". Data were obtained for Scotland from the Public Health Scotland "COVID19 wider impacts on the health care system" dashboard and for England from ImmForm. Five vaccinations delivered at different ages were evaluated; 3 doses of "6-in-1" diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, and hepatitis B vaccine (DTaP/IPV/Hib/HepB) and 2 doses of measles, mumps, and rubella (MMR) vaccine. This represented 439,754 invitations to be vaccinated in Scotland and 4.1 million for England. Uptake during the 2020 periods was compared to the previous year (2019) using binary logistic regression analysis. For Scotland, uptake within 4 weeks of a child becoming eligible by age was analysed along with geographical region and indices of deprivation. For Scotland and England, we assessed whether immunisations were up-to-date at approximately 6 months (all doses 6-in-1) and 16 to 18 months (first MMR) of age. We found that uptake within 4 weeks of eligibility in Scotland for all the 5 vaccines was higher during lockdown than in 2019. Differences ranged from 1.3% for first dose 6-in-1 vaccine (95.3 versus 94%, odds ratio [OR] compared to 2019 1.28, 95% confidence intervals [CIs] 1.18 to 1.39) to 14.3% for second MMR dose (66.1 versus 51.8%, OR compared to 2019 1.8, 95% CI 1.74 to 1.87). Significant increases in uptake were seen across all deprivation levels. In England, fewer children due to receive their immunisations during the lockdown period were up to date at 6 months (6-in-1) or 18 months (first dose MMR). The fall in percentage uptake ranged from 0.5% for first 6-in-1 (95.8 versus 96.3%, OR compared to 2019 0.89, 95% CI 0.86- to 0.91) to 2.1% for third 6-in-1 (86.6 versus 88.7%, OR compared to 2019 0.82, 95% CI 0.81 to 0.83). The use of routinely collected data used in this study was a limiting factor as detailed information on potential confounding factors were not available and we were unable to eliminate the possibility of seasonal trends in immunisation uptake. CONCLUSIONS: In this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.

Impact of the COVID-19 pandemic on Bordetella pertussis infections in England.

BACKGROUND: In March 2020, England went into its first lockdown in response to the COVID-19 pandemic. Restrictions eased temporarily, followed by second and third waves in October 2020 and January 2021. Recent data showed that the COVID-19 pandemic resulted in reduced transmission of some invasive diseases. We assess the impact of the COVID-19 pandemic on pertussis incidence and on the immunisation programme in England. METHODS: We assessed trends in pertussis cases from 2012 to 2020 by age group and month. Incidence from the time that England eased its initial lockdown measures in July 2020 through to summer 2021 was calculated and the incidence rate ratios of pertussis cases from five years prior to the pandemic (July 2014 - June 2019) compared to the same time period during the pandemic (July 2020 - June 2021). Vaccine coverage estimates for pertussis containing vaccines were reviewed for the maternal and childhood programmes. RESULTS: A substantial decline in pertussis cases was observed from April 2020 onwards, marking the lowest number of cases in the last decade. Pertussis incidence dropped in all age groups, particularly among infants less than one year old (0.50 / 100,000 during July 2020 to June 2021 compared to 24.49/ 100,000 from July 2014 to June 2019). The incidence rate ratio was 0.02 (95% CI 0.01 to 0.02) for July 2014 to June 2019 (pre-pandemic) compared to the pandemic period of July 2020 to June 2021. None of the cases had a co-infection with SARS-CoV-2. Vaccine coverage for infants born between January to March 2020 with three doses of pertussis vaccine by 12 months of age decreased by 1.1% points compared to infants born between January to March 2019 (91.6% and 92.7%, respectively). Prenatal pertussis coverage for the 2020 to 2021 financial year was 2.7% points lower than the year prior to the pandemic (70.5% and 76.8%, respectively). CONCLUSIONS: Lockdown measures due to the COVID-19 pandemic have had a significant impact on pertussis transmission. With the easing of restrictions it is important to continue monitoring pertussis cases in England alongside coverage of the maternal and childhood immunisation programmes.

Impact of Extending the Timing of Maternal Pertussis Vaccination on Hospitalized Infant Pertussis in England, 2014-2018.

BACKGROUND: In October 2012, a maternal pertussis vaccination program was introduced in England for women between 28 and 32 weeks of pregnancy. In April 2016, the recommended optimal window was extended to 20-32 weeks to improve vaccine coverage and protect preterm infants. This study assesses the impact of offering maternal pertussis vaccination earlier in pregnancy on hospitalized infant pertussis cases. METHODS: Hospitalized pertussis cases ≤60 days old in England were extracted from Hospital Episode Statistics pre- and post-policy change. Data were linked to laboratory-confirmed cases, and clinical records were reviewed where cases were not matched. Maternal vaccine status of identified cases was established. Median hospital duration was calculated, and a competing risk survival analysis was undertaken to assess multiple factors. RESULTS: A total of 201 cases were included in the analysis. Of the 151 cases with reported gestational age, the number of hospitalizations among full-term infants was 60 cases pre-policy and 62 cases post-policy, respectively, while preterm cases declined from 20 to 9 (P = .06). Length of hospital stay did not differ significantly after the policy change. Significantly longer hospital stays were seen in cases aged 0-4 weeks (median of 3 more days than infants aged 5-8 weeks), premature infants (median of 4 more days than term infants), and cases with coinfections (median of 1 more day than those without coinfection). CONCLUSIONS: The number of preterm infants hospitalized with pertussis in England was halved after the policy change and preterm infants were no longer overrepresented among hospitalized cases.

Investigation of a pertussis outbreak and comparison of two acellular booster pertussis vaccines in a junior school in South East England, 2019.

In March 2019, a pertussis outbreak occurred in children in a junior school (7-11 years) in England who had been offered pertussis-containing booster vaccine at 40 months of age. In a case-control investigation, we assessed the extent of transmission and any difference in protection afforded to those who had previously received a booster 3- or 5-component acellular pertussis vaccine (aP). We took oral fluid specimens from the students to determine IgG antibodies against pertussis toxin (anti-PT). Parents of students attending the school were sent a questionnaire on pertussis symptoms and vaccination status was retrieved from general practitioner records for all students. Of 381 students, 134 (35.2%) were classified as pertussis cases, 133 by demonstration of significant anti-PT IgG titres and one clinically. There was no significant difference in the risk of pertussis between students receiving 3-component (33.7%) or 5-component (32.3%) aP boosters. However, pertussis infection differed significantly in school year 4, with 22.9%, 50.0%, 23.7% and 38.1% pertussis cases in years 3, 4, 5 and 6, respectively. The proportion of students with incomplete vaccinations recorded was higher than the proportion of those not covered according to the national reported coverage, possibly contributing to sustained transmission within the school.

Surge in SARS-CoV-2 transmission in school-aged children and household contacts, England, August to October 2021.

Easing of COVID-19 restrictions in England in the summer of 2021 was followed by a sharp rise in cases among school-aged children. Weekly rates of SARS-CoV-2 infection in primary and secondary school children reached 733.3 and 1,664.7/100,000 population, respectively, by week 39 2021. A surge in household clusters with school-aged index cases was noted at the start of the school term, with secondary cases predominantly in children aged 5-15 years and adults aged 30-49 years.

The impact of social and physical distancing measures on COVID-19 activity in England: findings from a multi-tiered surveillance system.

BackgroundA multi-tiered surveillance system based on influenza surveillance was adopted in the United Kingdom in the early stages of the coronavirus disease (COVID-19) epidemic to monitor different stages of the disease. Mandatory social and physical distancing measures (SPDM) were introduced on 23 March 2020 to attempt to limit transmission.AimTo describe the impact of SPDM on COVID-19 activity as detected through the different surveillance systems.MethodsData from national population surveys, web-based indicators, syndromic surveillance, sentinel swabbing, respiratory outbreaks, secondary care admissions and mortality indicators from the start of the epidemic to week 18 2020 were used to identify the timing of peaks in surveillance indicators relative to the introduction of SPDM. This timing was compared with median time from symptom onset to different stages of illness and levels of care or interactions with healthcare services.ResultsThe impact of SPDM was detected within 1 week through population surveys, web search indicators and sentinel swabbing reported by onset date. There were detectable impacts on syndromic surveillance indicators for difficulty breathing, influenza-like illness and COVID-19 coding at 2, 7 and 12 days respectively, hospitalisations and critical care admissions (both 12 days), laboratory positivity (14 days), deaths (17 days) and nursing home outbreaks (4 weeks).ConclusionThe impact of SPDM on COVID-19 activity was detectable within 1 week through community surveillance indicators, highlighting their importance in early detection of changes in activity. Community swabbing surveillance may be increasingly important as a specific indicator, should circulation of seasonal respiratory viruses increase.

Infant Hospitalizations and Fatalities Averted by the Maternal Pertussis Vaccination Program in England, 2012-2017: Post-implementation Economic Evaluation.

In October 2012, a maternal pertussis vaccination program was implemented in England following an increased incidence and mortality in infants. We evaluated the cost-effectiveness of the program by comparing pertussis-related infant hospitalizations and deaths in 2012-2017 with nonvaccination scenarios. Despite considerable uncertainties, findings support the cost-effectiveness of the program.

Early impact of the coronavirus disease (COVID-19) pandemic and physical distancing measures on routine childhood vaccinations in England, January to April 2020.

Using electronic health records, we assessed the early impact of coronavirus disease (COVID-19) on routine childhood vaccination in England by 26 April 2020. Measles-mumps-rubella vaccination counts fell from February 2020, and in the 3 weeks after introduction of physical distancing measures were 19.8% lower (95% confidence interval: -20.7 to -18.9) than the same period in 2019, before improving in mid-April. A gradual decline in hexavalent vaccination counts throughout 2020 was not accentuated by physical distancing.

Human Exposures to H5N6 Avian Influenza, England, 2018.

The human risk following exposure to the European reassortant avian influenza A(H5N6) is unknown. We used routine data collected as part of public health follow-up to assess outcomes of individuals exposed to H5N6-infected wild birds in England. There were 19 separate incidents of confirmed H5N6 among wild birds in the first quarter of 2018 in England and 69 individuals exposed to infected birds during these incidents. Five exposed individuals developed respiratory symptoms. However, no H5N6 infection was detected among those individuals with respiratory symptoms who underwent diagnostic testing, indicating that the human risk from this strain remains low.

Uptake and impact of vaccinating primary school-age children against influenza: experiences of a live attenuated influenza vaccine programme, England, 2015/16.

The 2015/16 influenza season was the third season of the introduction of an intra-nasally administered live attenuated influenza vaccine (LAIV) for children in England. All children aged 2‒6 years were offered LAIV, and in addition, a series of geographically discrete areas piloted vaccinating school-age children 7‒11 years old. Influenza A(H1N1)pdm09 was the dominant circulating strain during 2015/16 followed by influenza B. We measured influenza vaccine uptake and the overall and indirect effect of vaccinating children of primary school -age, by comparing cumulative disease incidence in targeted and non-targeted age groups in vaccine pilot and non-pilot areas in England. Uptake of 57.9% (range: 43.6-72.0) was achieved in the five pilot areas for children aged 5‒11 years. In pilot areas, cumulative emergency department respiratory attendances, influenza-confirmed hospitalisations and intensive care unit admissions were consistently lower, albeit mostly non-significantly, in targeted and non-targeted age groups compared with non-pilot areas. Effect sizes were less for adults and more severe endpoints. Vaccination of healthy primary school-age children with LAIV at moderately high levels continues to be associated with population-level reductions in influenza-related respiratory illness. Further work to evaluate the population-level impact of the programme is required.

Mixture modelling of Bordetella pertussis serology samples to evaluate anti-pertussis toxin immunoglobulin G titre thresholds for positivity: England 2008-2022.

Introduction. Antibody testing for evidence of a recent Bordetella pertussis infection by estimating anti-pertussis toxin immunoglobulin G (anti-PT-IgG) titres by enzyme-linked immunosorbent assays is often recommended for those with a cough lasting more than 14 days. Interpreting results varies, with studies recommending different anti-PT-IgG titre thresholds for assigning positivity. In England, early work looking at antibody titre distributions for samples submitted from April 2010 to July 2012 found an optimal threshold of greater than 70 IU ml-1 for good sensitivity, specificity and positive predictive value.Aim. The aim of this study is to use the same mixture modelling technique to determine if the 70 IU ml-1 threshold remains appropriate when assessing data before, during and after the outbreak of pertussis in 2011-2012.Methods. We reviewed titres for all serology-tested samples in England between 1 July 2008 to 30 June 2022. IgG titres were used to calculate the positivity based on the current threshold of 70 IU ml-1, the median duration of cough for individuals who tested positive and, through mixture modelling, the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of assay thresholds.Results. Positivity rates increased from 21.7 % prior to the outbreak to 30.3 % during the outbreak and dropped to 25.1 % post-outbreak; similar to estimates from the mixture model of 20.5, 33.3 and 28.7 %, respectively. Although the estimated sensitivity dropped during and after the outbreak when applying the 70 IU ml-1 threshold, the PPV remained high and therefore no change to this threshold is warranted.Conclusion. Mixture modelling is a useful tool to establish thresholds, but reassessment should also be done when there have been changes to prevalence and/or testing regimes to determine whether there have been any changes in sensitivity, specificity, PPV, and NPV and whether the threshold should be revised.

Re-evaluation of the risk of venous thromboembolism after COVID-19 vaccination using haematological criteria.

An elevated risk of venous thromboembolism (VTE) following a first dose of the ChAdOx1 adenovirus-vectored vaccine was found in a national epidemiological study in England using routine discharge diagnosis codes. Separately, the syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) was identified using haematological criteria based on presence of thrombocytopenia, significantly elevated D-dimers and development of anti-PF4 antibodies. To re-evaluate risk estimates using haematological criteria, we obtained the haematology results for hospital admitted patients aged 18-64 years in 43 National Health Service trusts in England who were included in the national epidemiological study. Diagnoses were confirmed and haematological parameters obtained from local records without knowledge of vaccination status. The haematological parameters in patients admitted for a confirmed VTE following ChAdOx1 or BNT162b2 mRNA vaccination were then compared with those in a randomly selected 40% sample of unvaccinated patients with VTE. Overall, 12 (14%) of the 84 vaccinated cases had a diagnosis compatible with VITT, 11 after a first dose of ChAdOx1 and one after a first dose of BNT162b2. Thrombocytopenia (platelet count <150 × 109/L) occurred in 17 vaccinated (20%) and 4 (4%) of 108 unvaccinated patients, with all 6 cases of severe thrombocytopenia (<50 × 109/L) occurring within 42 days of a first dose of ChAdOx1. The attributable risk estimates for a cerebral venous thrombosis (CVT) or other VTE with thrombocytopenia after a first dose of ChAdOx1 vaccine were 2.82 and 9.62 per million doses respectively. However, elevated risks were also found after a first dose of ChAdOx1 for VTE without thrombocytopenia with relative incidences for CVT and other VTE of 2.67 (1.77-3.77) and 1.93 (1.57-2.35) respectively. While we identified a distinct population with features of VITT within 42 days of receiving ChAdOx1 vaccination, confirming current diagnostic criteria, we also found evidence of an increased risk of a VTE without thrombocytopenia after ChAdOx1 vaccine.