Serological outcomes of SARS-CoV-2 infection by vaccination status and variant in England (preprint)

Background Throughout the SARS-CoV-2 pandemic, several vaccines have been rolled out and distinct variants with different severity and immune profiles emerged in England. Using data from enhanced surveillance of COVID-19 in vaccine eligible individuals we investigated the antibody response following SARS-CoV-2 infection according to vaccination status and variant. Methods PCR-positive eligible individuals were identified from community PCR testing data in England between February 2021 and April 2022 and contacted by nurses to complete questionnaires at recruitment and 21 days post recruitment. Individuals were sent self-sampling kits and self-sampled nasal/oropharyngeal swabs were taken day 1, day 3 and day 7 post-recruitment as well as acute (day 1), convalescent (follow-up) serum and oral fluid samples. Regression analyses were used to investigate how N antibody seroconversion differs by vaccine status, and to investigate how N and S antibody levels differ by vaccine status overall and stratified by variants. Interval-censored analyses and regression analyses were used to investigate the effect of acute S antibody levels on the duration of positivity, the cycle threshold values, the self-reported symptom severity and the number of symptoms reported. Results A total of 1,497 PCR positive individuals were included. A total of 369 (24.7%) individuals were unvaccinated, 359 (24.0%) participants were infected with Alpha, 762 (50.9%) with Delta and 376 (25.2%) with Omicron. The median age of participants was 49 years old (IQR 39-57). Convalescent anti-N antibody levels were lower in vaccinated individuals and convalescent anti-S antibody levels were higher in vaccinated individuals and increased with the number of doses received. Acute anti-S antibody level increased with the number of doses received. Higher acute anti-S antibody levels were associated with a shorter duration of positivity (overall and for the Delta variant). Higher acute anti-S antibody levels were also associated with higher Ct values (overall and for the Alpha and Delta variants). There was no association between the acute anti-S antibody level and self-reported symptom severity. Individuals with higher acute anti-S antibody level were less likely to report six or more symptoms (overall and for Delta variant). Conclusion Understanding the characteristics of the antibody response, its dynamics over time and the immunity it confers is important to inform future vaccination strategies and policies. Our findings suggest that vaccination is associated with high acute anti-S antibody level but reduced convalescent anti-N antibody level. High anti-S antibody level is associated with reduced duration of infection, reduced infectiousness and may also be associated with reduced symptoms severity and number of symptoms.

Effectiveness of BNT162b2 and ChAdOx1 against SARS-CoV-2 household transmission - a prospective cohort study in England (preprint)

Background: The ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated effectiveness of BNT162b2 and ChAdOx1 vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England. Methods: Adult index cases in the community and their household contacts took oral-nasal swabs on days 1, 3 and 7 after enrolment. Swabs were tested by RT-qPCR with genomic sequencing conducted on a subset. We used Bayesian logistic regression to infer vaccine effectiveness against acquisition and transmission, adjusted for age, vaccination history and variant. Findings: Between 2 February 2021 and 10 September 2021 213 index cases and 312 contacts were followed up. After excluding households lacking genomic proximity (N=2) or with unlikely serial intervals (N=16), 195 households with 278 contacts remained of whom 113 (41%) became PCR positive. Delta lineages were 4.6 times (95% Credible Interval: 1.5 - 20.1) more transmissible than Alpha; contacts older than 18 years were 2.0 times (1.4 - 3.3) more likely to acquire infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 31% (-3%, 61%) and 42% (14%, 69%) for ChAdOx1, similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta, 71% (12%,95%) vs 24% (-2%, 64%) respectively for BNT162b2 and 26% (-39%, 73%) vs 14% (-5%, 46%) respectively for ChAdOx1. Interpretation: BNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting though their protection against infection is low. Funding: This study was funded by the UK Health Security Agency (formerly Public Health England) as part of the COVID-19 response.

Nucleocapsid antibody positivity as a marker of past SARS-CoV-2 infection in population serosurveillance studies: impact of variant, vaccination, and choice of assay cut-off (preprint)

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 titres 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.

Localising Vaccination Services: Qualitative Insights on an Orthodox Jewish Collaboration with Public health during the UK coronavirus Vaccine Programme (preprint)

Ethnic and religious minorities have been disproportionately affected by the SARS-CoV-2 pandemic and are less likely to accept coronavirus vaccinations. Orthodox (Haredi) Jewish neighbourhoods in England experienced high incidences of SARS-CoV-2 in 2020-21 and measles outbreaks (2018-19) due to suboptimal childhood vaccination coverage. The objective of our study was to explore how the coronavirus vaccination programme (CVP) was co-delivered between public health services and an Orthodox Jewish health organisation. Methods: included 28 semi-structured interviews conducted virtually with public health professionals, community welfare and religious representatives, and household members. We examined CVP delivery from the perspectives of those involved in organising services and vaccine beneficiaries. Interview data was contextualised within debates of the CVP in Orthodox (Haredi) Jewish print and social media. Thematic analysis generated five considerations: i) Prior immunisation-related collaboration with public health services carved a role for Jewish health organisations to host and promote coronavirus vaccination sessions, distribute appointments, and administer vaccines ii) Public health services maintained responsibility for training, logistics, and maintaining vaccination records; iii) The localised approach to service delivery promoted vaccination in a minority with historically suboptimal levels of coverage; iv) Co-delivery promoted trust in the CVP, though a minority of participants maintained concerns around safety; v) Provision of CVP information and stakeholders’ response to situated (context-specific) challenges and concerns. Drawing on this example of CVP co-delivery, we propose that a localised approach to delivering immunisation programmes could address service provision gaps in ways that involve trusted community organisations. Localisation of vaccination services can include communication or implementation strategies, but both approaches involve consideration of investment, engagement and coordination, which are not cost-neutral. Localising vaccination services in collaboration with welfare groups raises opportunities for the on-going CVP and other immunisation programmes, and constitutes an opportunity for ethnic and religious minorities to collaborate in safeguarding community health.

COVID-19 vaccination beliefs, attitudes, and behaviours among health and social care workers in the UK: a mixed-methods study (preprint)

BackgroundThe UK began delivering its COVID-19 vaccination programme on 8 December 2020, with health and social care workers (H&SCWs) given high priority for vaccination. Despite well- documented occupational exposure risks, however, there is evidence of lower uptake among some H&SCW groups. MethodsWe used a mixed-methods approach - involving an online cross-sectional survey and semi- structured interviews - to gain insight into COVID-19 vaccination beliefs, attitudes, and behaviours amongst H&SCWs in the UK by socio-demographic and employment variables. 1917 people were surveyed - 1658 healthcare workers (HCWs) and 261 social care workers (SCWs). Twenty participants were interviewed. FindingsWorkplace factors contributed to vaccination access and uptake. SCWs were more likely to not be offered COVID-19 vaccination than HCWs (OR:1.453, 95%CI: 1.244 - 1.696). SCWs specifically reported uncertainties around how to access COVID-19 vaccination. Participants who indicated stronger agreement with the statement I would recommend my organisation as a place to work were more likely to have been offered COVID-19 vaccination (OR:1.28, 95%CI: 1.06 - 1.56). Those who agreed more strongly with the statement I feel/felt under pressure from my employer to get a COVID-19 vaccine were more likely to have declined vaccination (OR:1.75, 95%CI: 1.27- 2.41). Interviewees that experienced employer pressure to get vaccinated felt this exacerbated their vaccine concerns and increased distrust. In comparison to White British and White Irish participants, Black African and Mixed Black African participants were more likely to not be offered (OR:2.011, 95%CI: 1.026 - 3.943) and more likely to have declined COVID-19 vaccination (OR:5.55, 95%CI: 2.29 - 13.43). Reasons for declining vaccination among Black African participants included distrust in COVID-19 vaccination, healthcare providers, and policymakers. ConclusionH&SCW employers are in a pivotal position to facilitate COVID-19 vaccination access, by ensuring staff are aware of how to get vaccinated and promoting a workplace environment in which vaccination decisions are informed and voluntary.

COVID-19 Outbreaks Following Full Reopening of Primary and Secondary Schools in England: Retrospective, Cross-Sectional National Surveillance (preprint)

Background: The full reopening of schools in September 2020 was associated with an increase in COVID-19 cases and outbreaks in educational settings across England. Methods: Primary and secondary schools reporting an outbreak (≥2 laboratory-confirmed cases within 14 days) to Public Health England (PHE) between 31 August and 18 October 2020 were contacted to complete an online questionnaire. Interpretation: There were 969 primary (n=450) and secondary school outbreaks (n=519) reported to PHE, representing 3% of primary schools and 15% of secondary schools in England. Of the 369 schools contacted, 190 geographically-representative schools completed the questionnaire; 2,425 cases were reported. Secondary school students (1.20%; 95%CI, 1.13-1.28%) had higher attack rates than primary school students (0.84%; 95%CI, 0.75-0.94%). Outbreaks were larger and across more year groups in secondary schools than in primary schools. When an outbreak occurred, attack rates were higher in staff (926/19,083; 4.85%; 95%CI, 4.55-5.17%) than students, especially among primary school teaching staff (9.81%; 95%CI, 8.90-10.82%) compared to secondary school teaching staff (3.97%; 95%CI, 3.79-5.69%). Staff represented 59% (471/799) of cases in primary school outbreaks and 27% (410/1515) in secondary schools (P<0.001). Teaching staff were more likely to be the index case in primary (48/100, 48%) than in secondary (25/79, 32%) schools (P=0.027).Conclusions: Secondary schools were more likely to be affected by a COVID-19 outbreak than primary schools and to experience larger outbreaks across multiple school years. The higher attack rate among teaching staff during an outbreak suggests that additional protective measures may be needed. Funding: PHE

Prospective Active National Surveillance of Preschools and Primary Schools for SARS-CoV-2 Infection and Transmission in England, June 2020: (sKIDs: COVID-19 Surveillance in School KIDs) (preprint)

Background: Many countries re-opened schools after national lockdown but little is known about the risk of SARS-CoV-2 infection and transmission in educational settings. Public Health England conducted six-month prospective surveillance in primary schools across England. Methods: The COVID-19 Surveillance in School KIDs (sKIDs) study included two arms: weekly nasal swabs for ≥4 weeks following partial reopening during the summer half-term (June to mid-July 2020) and blood sampling with nasal and throat swabs at the beginning and end of the summer half-term, and, following full reopening in September 2020, at the end of the autumn term (end-November 2020). Results: In round 1, 12,026 participants (59.1% students, 40.9% staff) in 131 schools had 43,091 swabs taken. Weekly SARS-CoV-2 infection rates were 3.9 (1/25,537; 95% CI, 0.10-21.8) and 11.3 (2/17,554; 95% CI, 1.4-41.2) per 100,000 students and staff. At recruitment, N-antibody positivity in 45 schools was 11.1% (91/817; 95%CI, 9.2-13.5%) in students and 15.1% (209/1381; 95%CI, 13.3-17.1%) in staff, similar to local community seroprevalence. Seropositivity was not associated with school attendance during lockdown or staff contact with students. Round 2 participation was 73.7% (1,619/2,198) and only five (4 students, 1 staff) seroconverted. In round 3, when 61.9% (1,361/2,198) of round 1 participants were re-tested, seroconversion rates were 3.4% (19/562; 95%CI, 2.0-5.2) in students and 3.9% (36/930; 95%CI, 2.7-5.3) in staff. Conclusions: SARS-CoV-2 infection rates, assessed using nasal swabs for acute infection and serum antibodies for prior infection, were low following partial and full reopening of primary schools in England.Funding Statement: This surveillance was funded by the Department of Health and Social Care (DHSC).Declaration of Interests: None to declare.Ethics Approval Statement: The surveillance protocol was approved by the Public Health England Research Ethics Governance Group (R&D REGG Ref: NR0209, 16 May 2020).

COVID-19 Outbreaks Following Full Reopening of Primary and Secondary Schools in England: Retrospective, Cross-Sectional National Surveillance (preprint)

Background: The full reopening of schools in September 2020 was associated with an increase in COVID-19 cases and outbreaks in educational settings across England.Methods: Primary and secondary schools reporting an outbreak (≥2 laboratory-confirmed cases within 14 days) to Public Health England (PHE) between 31 August and 18 October 2020 were contacted to complete an online questionnaire.Interpretation: There were 969 primary (n=450) and secondary school outbreaks (n=519) reported to PHE, representing 3% of primary schools and 15% of secondary schools in England. Of the 369 schools contacted, 190 geographically-representative schools completed the questionnaire; 2,425 cases were reported. Secondary school students (1.20%; 95%CI, 1.13-1.28%) had higher attack rates than primary school students (0.84%; 95%CI, 0.75-0.94%). Outbreaks were larger and across more year groups in secondary schools than in primary schools. When an outbreak occurred, attack rates were higher in staff (926/19,083; 4.85%; 95%CI, 4.55-5.17%) than students, especially among primary school teaching staff (378/3852; 9.81%; 95%CI, 8.90-10.82%) compared to secondary school teaching staff (284/7146; 3.97%; 95%CI, 3.79-5.69%). Staff represented 59% (471/799) of cases in primary school outbreaks and 27% (410/1515) in secondary schools (P<0.001). Teaching staff were more likely to be the index case in primary (48/100, 48%) than in secondary (25/79, 32%) schools (P=0.027). Conclusions: Secondary schools were more likely to be affected by a COVID-19 outbreak than primary schools and to experience larger outbreaks across multiple school years. The higher attack rate among teaching staff during an outbreak suggests that additional protective measures may be needed.Funding Statement: This surveillance was internally funded by PHE and did not receive any specific grant funding from agencies in the public, commercial or not-for-profit sectors.Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: PHE has legal permission, provided by Regulation 3 of The Health Service (Control of Patient Information) Regulations 2002, to process patient confidential information for national surveillance of communicable diseases and as such, individual patient consent is not required.

Transmission dynamics of COVID-19 in household and community settings in the United Kingdom (preprint)

Background: Households appear to be the highest risk setting for transmission of COVID-19. Large household transmission studies were reported in the early stages of the pandemic in Asia with secondary attack rates ranging from 5-30% but few large scale household transmission studies have been conducted outside of Asia. Methods: A prospective case ascertained study design based on the World Health Organization FFX protocol was undertaken in the UK following the detection of the first case in late January 2020. Household contacts of cases were followed using enhanced surveillance forms to establish whether they developed symptoms of COVID-19, became confirmed cases and their outcomes. Household secondary attack rates and serial intervals were estimated. Individual and household basic reproduction numbers were also estimated. The incubation period was estimated using known point source exposures that resulted in secondary cases. Results: A total of 233 households with two or more people were included with a total of 472 contacts. The overall household SAR was 37% (95% CI 31-43%) with a mean serial interval of 4.67 days, an R0 of 1.85 and a household reproduction number of 2.33. We find lower secondary attack rates in larger households. SARs were highest when the primary case was a child. We estimate a mean incubation period of around 4.5 days. Conclusions: High rates of household transmission of COVID-19 were found in the UK emphasising the need for preventative measures in this setting. Careful monitoring of schools reopening is needed to monitor transmission from children.

COVID-19 in Great Britain: epidemiological and clinical characteristics of the first few hundred (FF100) cases: a descriptive case series and case control analysis (preprint)

Objectives: Following detection of the first virologically-confirmed cases of COVID-19 in Great Britain, an enhanced surveillance study was initiated by Public Health England to describe the clinical presentation, course of disease and identify risk factors for infection of the first few hundred cases. Methods: Information was collected on the first COVID-19 cases according to the First Few X WHO protocol. Case-control analyses of the sensitivity, specificity and predictive value of symptoms and risk factors for infection were conducted. Point prevalences of underlying health conditions among the UK general population were presented. Findings: The majority of FF100 cases were imported (51.4%), of which the majority had recent travel to Italy (71.4%). 24.7% were secondary cases acquired mainly through household contact (40.4%). Children had lower odds of COVID-19 infection compared with the general population. The clinical presentation of cases was dominated by cough, fever and fatigue. Non-linear relationships with age were observed for fever, and sensitivity and specificity of symptoms varied by age. Conditions associated with higher odds of COVID-19 infection (after adjusting for age and sex) were chronic heart disease, immunosuppression and multimorbidity. Conclusion: This study presents the first epidemiological and clinical summary of COVID-19 cases in Great Britain. The FFX study design enabled systematic data collection. The study was able to characterize the risk factors for infection with population prevalence estimates setting these relative risks into a public health context. It also provides important evidence for generating case definitions to support public health risk assessment, clinical triage and diagnostic algorithms.