Seroprevalence of SARS-CoV-2 Antibodies in University Students: Cross-sectional Study, December 2020, England (preprint)

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.

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

Do antibody positive healthcare workers have lower SARS-CoV-2 infection rates than antibody negative healthcare workers? Large multi-centre prospective cohort study (the SIREN study), England: June to November 2020 (preprint)

BackgroundThere is an urgent need to better understand whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection. MethodsA large multi-centre prospective cohort was recruited from publicly funded hospital staff in the UK. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2-4 weeks) and completed fortnightly questionnaires on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive or prior PCR/antibody test positive) or negative cohort (antibody negative, not previously known to be PCR/antibody positive). Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, possible (subdivided by symptom-status)) depending on hierarchy of evidence. Individuals in the primary infection were excluded from this analysis if infection was confirmed by antibody only. Reinfection rates in the positive cohort were compared against new PCR positives in the negative cohort using a mixed effective multivariable logistic regression analysis. FindingsBetween 18 June and 09 November 2020, 44 reinfections (2 probable, 42 possible) were detected in the baseline positive cohort of 6,614 participants, collectively contributing 1,339,078 days of follow-up. This compares with 318 new PCR positive infections and 94 antibody seroconversions in the negative cohort of 14,173 participants, contributing 1,868,646 days of follow-up. The incidence density per 100,000 person days between June and November 2020 was 3.3 reinfections in the positive cohort, compared with 22.4 new PCR confirmed infections in the negative cohort. The adjusted odds ratio was 0.17 for all reinfections (95% CI 0.13-0.24) compared to PCR confirmed primary infections. The median interval between primary infection and reinfection was over 160 days. InterpretationA prior history of SARS-CoV-2 infection was associated with an 83% lower risk of infection, with median protective effect observed five months following primary infection. This is the minimum likely effect as seroconversions were not included. FundingDepartment of Health and Social Care and Public Health England, with contributions from the Scottish, Welsh and Northern Irish governments.

SIREN protocol: Impact of detectable anti-SARS-CoV-2 on the subsequent incidence of COVID-19 in 100,000 healthcare workers: do antibody positive healthcare workers have less reinfection than antibody negative healthcare workers? (preprint)

BACKGROUND The overall risk of reinfection in individuals who have previously had COVID-19 is unknown. To determine if prior SARS-CoV-2 infection (as determined by at least one positive commercial antibody test performed in a laboratory) in healthcare workers confers future immunity to reinfection, we are undertaking a large-scale prospective longitudinal cohort study of healthcare staff across the United Kingdom. METHODS Population and Setting: staff members of healthcare organisations working in hospitals in the UK At recruitment, participants will have their serum tested for anti-SARS-CoV-2 at baseline and using these results will be initially allocated to either antibody positive or antibody negative cohorts. Participants will undergo antibody and viral RNA testing at 1-4 weekly intervals throughout the study period, and based on these results may move between cohorts. Any results from testing undertaken for other reasons (e.g. symptoms, contact tracing etc.) or prior to study entry will also be included. Individuals will complete enrolment and fortnightly questionnaires on exposures and symptoms. Follow-up will be for at least 12 months from study entry. Outcome: The primary outcome of interest is a reinfection with SARS -CoV-2 during the study period. Secondary outcomes will include incidence and prevalence (both RNA and antibody) of SARS-CoV-2, viral genomics, viral culture, symptom history and antibody/neutralising antibody titres. CONCLUSION This large study will help us to understand the impact of the presence of antibodies on the risk of reinfection with SARS-CoV-2; the results will have substantial implications in terms of national and international policy, as well as for risk management of contacts of COVID-19 cases. TRIAL REGISTRATION IRAS ID 284460, HRA and Health and Care Research Wales approval granted 22 May 2020.

High Prevalence of SARS-CoV-2 Antibodies in Care Homes Affected by COVID-19; Prospective Cohort Study, England (preprint)

Background: We investigated six London care homes experiencing a COVID-19 outbreak and found very high rates of SARS-CoV-2 infection among residents and staff. Here we report follow-up investigations including antibody testing in the same care homes five weeks later.Methods: Residents and staff involved 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, 208/241 (86.3%) surviving residents and 186/254 (73.2%) staff underwent repeat testing. Almost all SARS-CoV-2 RT-PCR positive residents and staff were also antibody positive five weeks later, whether symptomatic (residents 35/35, 100%; staff, 22/22, 100%) or asymptomatic (residents 32/33, 97.0%; staff 21/22, 95.1%). Symptomatic but SARS-CoV-2 RT-PCR negative residents and staff also had high seropositivity rates (residents 23/27, 85.2%; staff 18/21, 85.7%) as did asymptomatic RT-PCR negative individuals (residents 62/92, 67.3%; staff 95/143, 66.4%). Neutralising antibody was present in 118/132 (89.4%) seropositive individuals and was not associated with age or symptoms. Ten residents (10/108, 9.3%) remained RT-PCR positive but with lower RT-PCR cycle threshold values; all 7 tested were seropositive. New infections were detected in three residents and one staff.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: NoneDeclaration of Interests: None.Ethics Approval Statement: The research protocol was approved by the PHE Research Ethics and Governance Group (REGG Ref: NR0204, 07 May 2020).

Investigation of SARS-CoV-2 Outbreaks in Six Care Homes in London, April 2020: The London Care Home Investigation (preprint)

Background: Care homes are experiencing large outbreaks of coronavirus disease 2019 (COVID-19) associated with high case-fatality. We conducted detailed investigations in six London care homes reporting suspected COVID-19 outbreaks during April 2020. Methods: Residents and staff had nasal swabs taken for SARS CoV-2 testing using RT-PCR and were followed-up for 14 days. They were categorized as symptomatic, post-symptomatic or pre-symptomatic if they had symptoms at the time of testing, in the two weeks before or two weeks after testing, respectively, or asymptomatic throughout. Virus isolation and whole genome sequencing (WGS) was also performed. Findings: Across the six care homes, 107/268 (39.9%) residents were SARS CoV-2 positive, including 29 (27.1%) symptomatic, 9 (8.4%) post-symptomatic, 21 (19.6%) pre-symptomatic and 48 (44.9%) who remained asymptomatic. Case-fatality was highest among symptomatic SARS-CoV-2 positive residents (10/29, 34.5%) compared to asymptomatic (2/48, 4.2%), post-symptomatic (2/9, 22.2%) or pre-symptomatic (3/21,14.3%) residents. Among staff, 51/250 (20.4%) were SARS CoV-2 positive and 29/51 (56.9%) remained asymptomatic. RT-PCR cycle threshold s and live virus recovery were similar between symptomatic/asymptomatic residents/staff. WGS identified multiple introductions of different SARS-CoV-2 strains into individual care homes. SARS-CoV-2 strains from residents and staff had identical sequences, as did strains from fatal and non-fatal cases. Interpretation: In care homes reporting a COVID-19 outbreak, a high rate of SARS-CoV-2 positivity was found among residents and staff, half of whom were asymptomatic and are potential reservoirs for on-going transmission. Symptomatic SARS-CoV-2 residents had high case-fatality, while asymptomatic infection was rarely fatal. Symptom-based screening alone is not sufficient for outbreak control.Funding Statement: This study did not receive any funding. The authors are all employed by Public Health England, the study funder, which is a public body — an executive agency of the Department of Health. Declaration of Interests: None.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.

High prevalence of SARS-CoV-2 antibodies in care homes affected by COVID-19; a prospective cohort study in England (preprint)

Background: We investigated six London care homes experiencing a COVID-19 outbreak and found very high rates of SARS-CoV-2 infection among residents and staff. Here we report follow-up serological analysis in these care homes five weeks later. Methods: Residents and staff had a convalescent blood sample for SARS-CoV-2 antibody levels and neutralising antibodies by SARS-COV-2 RT-PCR five weeks after the primary COVID-19 outbreak investigation. Results: Of the 518 residents and staff in the initial investigation, 208/241 (86.3%) surviving residents and 186/254 (73.2%) staff underwent serological testing. Almost all SARS-CoV-2 RT-PCR positive residents and staff were antibody positive five weeks later, whether symptomatic (residents 35/35, 100%; staff, 22/22, 100%) or asymptomatic (residents 32/33, 97.0%; staff 21/22, 95.1%). Symptomatic but SARS-CoV-2 RT-PCR negative residents and staff also had high seropositivity rates (residents 23/27, 85.2%; staff 18/21, 85.7%), as did asymptomatic RT-PCR negative individuals (residents 62/92, 67.3%; staff 95/143, 66.4%). Neutralising antibody was present in 118/132 (89.4%) seropositive individuals and was not associated with age or symptoms. Ten residents (10/108, 9.3%) remained RT-PCR positive, but with lower RT-PCR cycle threshold values; all 7 tested were seropositive. New infections were detected in three residents and one staff member. Conclusions: RT-PCR testing for SARS-CoV-2 significantly underestimates the true extent of an outbreak in institutional settings. Elderly frail residents and younger healthier staff were equally able to mount robust and neutralizing antibody responses to SARS-CoV-2. More than two-thirds of residents and staff members had detectable antibodies against SARS-CoV-2 irrespective of their nasal swab RT-PCR positivity or symptoms status.