A cross-sectional national investigation of COVID-19 outbreaks in nurseries during rapid spread of the Alpha (B.1.1.7) variant of SARS- CoV-2 in England (preprint)

Background: In England, the emergence the more transmissible SARS-CoV-2 variant Alpha (B.1.1.7) led to a third national lockdown from December 2020, including restricted attendance at schools. Nurseries, however, remained fully open. COVID-19 outbreaks (≥ 2 laboratory-confirmed cases within 14 days) in nurseries and assess the risk of SARS-CoV-2 infection and incidence rates in staff and children over a three-month period when community SARS-CoV-2 infections rates were high and the Alpha variant was spreading rapidly across England. Methods This was a cross-sectional national investigation of COVID-19 outbreaks in nurseries across England Nurseries reporting a COVID-19 outbreak to PHE between November 2020 and January 2021 were requested to complete a questionnaire about their outbreak. Results 324 nurseries, comprising 1% (324/32,852) of nurseries in England, reported a COVID-19 outbreak. Of the 315 (97%) nurseries contacted, 173 (55%) reported 1,657 SARS-CoV-2 cases, including 510 (31%) children and 1,147 (69%) staff. A child was the index case in 45 outbreaks (26%) and staff in 125 (72%) outbreaks. Overall, children had an incidence rate of 3.50% (95%CI, 3.21–3.81%) and was similar irrespective of whether the index case was a child (3.55%; 95%CI, 3.01–4.19%) or staff (3.44%; 95%CI, 3.10–3.82%). Among staff, incidence rates were lower if the index case was a child (26.28%; 95%CI, 23.54–29.21%%) compared to a staff member (32.98%; 95%CI, 31.19–34.82%), with the highest incidence rate when the index case was also a staff member (37.52%; 95%CI, 35.39–39.70%). Compared to November 2020, outbreak sizes and incidence rates were higher in January 2021, when the Alpha variant predominated. Nationally, SARS-CoV-2 infection rates in

Emergence of the Delta Variant and risk of SARS-CoV-2 infection in secondary school students and staff: prospective surveillance in 18 schools, England (preprint)

Background The role of educational settings on SARS-CoV-2 infection and transmission remains controversial. We investigated SARS-CoV-2 infection, seroprevalence and seroconversions rates in secondary schools during the 2020/21 academic year, which included the emergence of the more transmissible Alpha and Delta variants, in England. Methods The UK Health Security Agency (UKHSA) initiated prospective surveillance in 18 urban English secondary schools. Participants had nasal swabs for SARS-CoV-2 RT-PCR and blood sampling for SARS-CoV-2 Nucleoprotein and Spike protein antibodies at the start (Round 1: September-October 2020) and end (Round 2: December 2021) of the autumn term, when schools reopened after national lockdown was imposed in January 2021 (Round 3: March-April) and end of the academic year (Round 4: May-July). Findings We enrolled 2,314 participants (1277 students, 1037 staff). In-school testing identified 31 PCR-positive participants (20 students, 11 staff). Another 247 confirmed cases (112 students, 135 staff) were identified after linkage with national surveillance data, giving an overall positivity rate of 12.0% (278/2313; staff [14.1%, 146/1037] vs students [10.3%, 132/1276; p=0.006). Nucleoprotein-antibody seroprevalence increased for students and staff between Rounds 1-3 but changed little in Round 4, when the Delta variant was the dominant circulating strain. Overall, Nucleoprotein-antibody seroconversion was 18.4% (137/744) in staff and 18.8% (146/778) in students, while Spike-antibody seroconversion was higher in staff (72.8% (525/721) than students (21.3%, 163/764) because of vaccination. Interpretation SARS-CoV-2 infection and transmission in secondary schools remained low when community infection rates were low because of national lockdown, even after the emergence of the Delta variant

Secondary Attack Rates in Primary and Secondary School Bubbles Following a Confirmed Case: Active, Prospective National Surveillance, November to December 2020, England (preprint)

Background: Following the full re-opening of schools in England and emergence of the SARS-CoV-2 Alpha variant, we investigated the risk of SARS-CoV-2 infection in students and staff who were contacts of a confirmed case in a school bubble (school groupings with limited interactions), along with their household members. Methods: Primary and secondary school bubbles were recruited into sKIDsBUBBLE after being sent home to self-isolate following a confirmed case of COVID-19 in the bubble. Bubble participants and their household members were sent home-testing kits comprising nasal swabs for RT-PCR testing and whole genome sequencing, and oral fluid swabs for SARS-CoV-2 antibodies. Results: During November-December 2020, 14 bubbles were recruited from 7 schools, including 269 bubble contacts (248 students, 21 staff) and 823 household contacts (524 adults, 299 children). The secondary attack rate was 10.0% (6/60) in primary and 3.9% (4/102) in secondary school students, compared to 6.3% (1/16) and 0% (0/1) among staff, respectively. The incidence rate for household contacts of primary school students was 6.6% (12/183) and 3.7% (1/27) for household contacts of primary school staff. In secondary schools, this was 3.5% (11/317) and 0% (0/1), respectively. Household contacts were more likely to test positive if their bubble contact tested positive although there were new infections among household contacts of uninfected bubble contacts. Interpretation: Compared to other institutional settings, the overall risk of secondary infection in school bubbles and their household contacts was low. Our findings are important for developing evidence-based infection prevention guidelines for educational settings.

Perceptions of Adolescents on the COVID-19 Pandemic and Returning to School: Qualitative Questionnaire Survey, England 2020 (preprint)

Background : Little is known about the views of adolescents returning to secondary school during the current COVID-19 pandemic. Methods: In September 2020, Public Health England (PHE) recruited staff and students in secondary schools to provide nasal swabs, oral fluid and blood samples for SARS-CoV-2 infection and antibody testing. Students aged 11-18 years in five London schools completed a short questionnaire about their perception of the pandemic, returning to school, risk to themselves and to others and infection control measures, and participating in school testing. Results: A questionnaire was completed by 64% (297/462) participants. Students were generally not anxious at all (19.7%; 58/294) or not really anxious (40.0%, 114/295) about returning to school, although 5.4% (n=16/295) were extremely nervous. Most students were very worried about transmitting the virus to their family (60.2%; 177/294) rather than other students (22.0%; 65/296) or school staff (19.3%; 57/296), or catching the infection themselves (12.5%; 37/296). Students better maintained physical distancing in the presence of school staff (84.6%; 247/292) and in public places (79.5%; 233/293) but not when with other students (46.8%; 137/293) or friends (40.8%; 120/294). A greater proportion of younger students (school years 7-9) reported not being anxious at all than 16-18 year olds (47/174 [27.0%] vs 3/63 [4.8%]; p=0.001). They were also less likely to adhere to physical distancing and wearing face masks. Most students reported positive experiences with testing in schools, with 92.3% (262/284) agreeing to have another blood test in future visits.Conclusions: Younger students were less concerned about catching and transmitting SARS-CoV-2 and were less likely to adhere to protective measures. Greater awareness of the potential risks of COVID-19 transmission between secondary school students potentially leading to increased risk of infection in their teachers and their household members may increase adherence to infection control measures within and outside schools.

Emergence of SARS-CoV-2 Alpha (B.1.1.7) variant, infection rates, antibody seroconversion and seroprevalence rates in secondary school students and staff: active prospective surveillance, December 2020 to March 2021, England (preprint)

Background In England, the rapid spread of the SARS-Cov-2 Alpha (B.1.1.7) variant from November 2020 led to national lockdown, including school closures in January 2021. We assessed SARS-CoV-2 infection, seroprevalence and seroconversion in students and staff when secondary schools reopened in March 2021. Methods Public Health England initiated SARS-CoV-2 surveillance in 18 secondary schools across six regions in September 2020. Participants provided nasal swabs for RT-PCR and blood samples for SARS-CoV-2 antibodies at the beginning (September 2020) and end (December 2020) of the autumn term and at the start of the spring term (March 2021). Findings In March 2021, 1895 participants (1100 students, 795 staff) were tested; 5.6% (61/1094) students and 4.4% (35/792) staff had laboratory-confirmed SARS-CoV-2 infection between December 2020 and March 2021. Nucleoprotein antibody seroprevalence was 36.3% (370/1018) in students and 31.9% (245/769) in staff, while spike protein antibody prevalence was 39.5% (402/1018) and 59.8% (459/769), respectively, similar to regional community seroprevalence. Between December 2020 and March 2021 (median 15.9 weeks), 14.8% (97/656; 95% CI: 12.2-17.7) students and 10.0% (59/590; 95% CI: 7.7-12.7) staff seroconverted. Weekly seroconversion rates were similar from September to December 2020 (8.0/1000) and from December 2020 to March 2021 (7.9/1000; students: 9.3/1,000; staff: 6.3/1,000). Interpretation By March 2021, a third of secondary school students and staff had serological evidence of prior infection based on N-antibody seropositivity, and an additional third of staff had evidence of vaccine-induced immunity based on S-antibody seropositivity. Further studies are needed to assess the impact of the Delta variant. Research in Context Evidence Before this study The Alpha variant is 30-70% more transmissible than previously circulating SARS-CoV-2 strains in adults and children. One outbreak investigation in childcare settings estimated similar secondary attack rates with the Alpha variant in children and adults. There are limited data on the impact of the Alpha variant in educational settings. In England, cases in primary and secondary school aged children increased rapidly from late November 2020 and peaked at the end of December 2020, leading to national lockdown including school closures. Added Value of This Study Seroconversion rates in staff and students during December 2020 to March 2021, when the Alpha variant was the primary circulating strain in England, were similar to the period between September 2020 and December 2020 when schools were fully open for in-person teaching. By March 2021, a third of students overall and more than half the students in some regions were seropositive for SARS-CoV-2 antibodies. Among staff, too, around a third had evidence of prior infection on serological testing and a further third had vaccine-induced immunity. Implications of all the Available Evidence SARS-CoV-2 antibody seroprevalence was high among secondary school students in March 2021 and is likely to be higher following the emergence of an even more transmissible Delta variant in May 2021. Education staff are increasingly being protected by the national COVID-19 immunisation programme. These findings have important implications for countries that are considering vaccination of children to control the pandemic

Implementation of COVID-19 Preventive Measures in Primary and Secondary Schools Following Reopening of Schools in Autumn 2020; A Cross-Sectional Study of Parents' and Teachers' Experiences in England (preprint)

Objective The main objective was to assess implementation of and ease of implementation of control measures in schools as reported by staff and parents. Design Cross-sectional study. Setting Staff and parents/guardian participants in the 132 primary schools and 20 secondary schools participating in sKIDs and sKIDsPLUS surveillances. Main outcome measure Prevalence of control measures implemented in Autumn 2020, parental and staff perception of ease of implementation and acceptability of conducting school surveillance studies. Results In total, 56/152 (37%) schools participating in Public Health England's sKIDs study of COVID in schools accepted the invitation to participate in the survey. By 28 December 2020, 1,953 parent and 986 staff respondents had completed the online questionnaire. While more than half the parents were positive about their children returning to school, roughly a third reported being a little anxious. 90% and 82% of primary and secondary school parents were either completely or partly reassured by the preventive measures implemented in their schools. Among staff, 80% of primary staff and 87% of secondary school staff felt that they were at higher risk of COVID-19 because of their profession; only 52% of primary school staff and 38% of secondary school staff reportedly felt safe. According to the teaching staff, most preventive measures were well-implemented apart from requiring 2-metre distancing between staff. For students, maintaining the 2-metre distance was reported to be particularly difficult. By extension, secondary schools also struggled to maintain small groups at all times or ensuring that the same staff were assigned to each student group (a problem also commonly reported by parents). Conclusions Variable implementation of infection control measures was reported by staff and parents. Whilst the majority were not worried about returning to school, some parents and staff, were concerned about returning to school and the risks posed to children, staff and household members.

Children develop strong and sustained cross-reactive immune responses against spike protein following SARS-CoV-2 infection (preprint)

SARS-CoV-2 infection is generally mild or asymptomatic in children but the biological basis for this is unclear. We studied the profile of antibody and cellular immunity in children aged 3-11 years in comparison with adults. Antibody profiles in children were strong with high titres against spike protein and receptor binding domain (RBD). SARS-CoV-2 seroconversion in children strongly boosted antibody responses against seasonal beta-coronaviruses, partly through cross-recognition of the S2 domain, indicating a broad humoral response that was not seen in adults. T cell responses against spike were also >2-fold higher in children compared to adults and displayed a strong Th1 cytokine profile. SARS-CoV-2 spike-reactive cellular responses were present in more than half the seronegative children, indicating pre-existing cross-reactive responses or sensitization against SARS-CoV-2. Importantly, all children retained high antibody titres and cellular responses for more than 6 months after infection whilst relative antibody waning was seen in adults. Children thus distinctly generate robust, cross-reactive and sustained immune responses after SARS-CoV-2 infection with focussed specificity against spike protein. These observations demonstrate several novel features of SARS-CoV-2-specific immune responses in children and may provide insights into relative clinical protection in this group. Such information on the profile of natural infection will help to guide the introduction of vaccination regimens into the paediatric population.

COVID-19 Outbreaks in Nurseries During Rapid Spread of the B.1.1.7 Variant of SARS-CoV-2 in England: Cross-Sectional National Surveillance, November 2020 – January 2021 (preprint)

Background: The reopening of schools during the COVID-19 pandemic has raised concerns about widespread infection and transmission of SARS-CoV-2 in educational settings. In June 2020, Public Health England (PHE) initiated prospective national surveillance of SARS-CoV-2 in primary schools across England (sKIDs). We used this opportunity to assess the feasibility and agreeability of large-scale surveillance and testing for SARS-CoV-2 infections in school among staff, parents and students.Methods: Staff and students in 131 primary schools were asked to complete a questionnaire at recruitment and provide weekly nasal swabs for SARS-CoV-2 RT-PCR testing (n=86) or swabs with blood samples for antibody testing (n=45) at the beginning and end the summer half-term. In six blood sampling schools, students were asked to complete a pictorial questionnaire before and after their investigations.Results: In total, 134 children aged 4-7 years (n=40) or 8-11 years (n=95) completed the pictorial questionnaire fully or partially. Prior to sampling, oral fluid sampling was the most acceptable test (107/132, 81%) followed by throat swabs (80/134, 59%), nose swabs (77/132, 58%), and blood tests (48/130, 37%). Younger students were more nervous about all tests than older students but, after completing their tests, most children reported a “better than expected” experience with all the investigations. Students were more likely to agree to additional testing for nose swabs (93/113, 82%) and oral fluid (93/114, 82%), followed by throat swabs (85/113, 75%) and blood tests (72/108, 67%). Parents (n=3,994) and staff (n=2,580) selected a preference for weekly testing with nose swabs, throat swabs or oral fluid sampling, although staff were more flexible about testing frequency. Conclusions: Primary school staff and parents were supportive of regular tests for SARS-CoV-2 and selected a preference for weekly testing. Children preferred nose swabs and oral fluids over throat swabs or blood sampling.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: 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.

Feasibility and Acceptability of SARS-CoV-2 Testing and Surveillance in Primary School Children in England (preprint)

Background: The reopening of schools during the COVID-19 pandemic has raised concerns about widespread infection and transmission of SARS-CoV-2 in educational settings. In June 2020, Public Health England (PHE) initiated prospective national surveillance of SARS-CoV-2 in primary schools across England (sKIDs). We used this opportunity to assess the feasibility and agreeability of large-scale surveillance and testing for SARS-CoV-2 infections in school among staff, parents and students.Methods: Staff and students in 131 primary schools were asked to complete a questionnaire at recruitment and provide weekly nasal swabs for SARS-CoV-2 RT-PCR testing (n=86) or swabs with blood samples for antibody testing (n=45) at the beginning and end the summer half-term. In six blood sampling schools, students were asked to complete a pictorial questionnaire before and after their investigations.Results: In total, 134 children aged 4-7 years (n=40) or 8-11 years (n=95) completed the pictorial questionnaire fully or partially. Prior to sampling, oral fluid sampling was the most acceptable test (107/132, 81%) followed by throat swabs (80/134, 59%), nose swabs (77/132, 58%), and blood tests (48/130, 37%). Younger students were more nervous about all tests than older students but, after completing their tests, most children reported a “better than expected” experience with all the investigations. Students were more likely to agree to additional testing for nose swabs (93/113, 82%) and oral fluid (93/114, 82%), followed by throat swabs (85/113, 75%) and blood tests (72/108, 67%). Parents (n=3,994) and staff (n=2,580) selected a preference for weekly testing with nose swabs, throat swabs or oral fluid sampling, although staff were more flexible about testing frequency. Conclusions: Primary school staff and parents were supportive of regular tests for SARS-CoV-2 and selected a preference for weekly testing. Children preferred nose swabs and oral fluids over throat swabs or blood sampling.

Characterising long COVID more than 6 months after acute infection in adults; prospective longitudinal cohort study, England (preprint)

Background Most individuals with COVID-19 will recover without sequelae, but some will develop long-term multi-system impairments. The definition, duration, prevalence and symptoms associated with long COVID, however, have not been established. Methods Public Health England (PHE) initiated longitudinal surveillance of clinical and non-clinical healthcare workers for monthly assessment and blood sampling for SARS-CoV-2 antibodies in March 2020. Eight months after enrolment, participants completed an online questionnaire including 72 symptoms in the preceding month. Symptomatic mild-to-moderate cases with confirmed COVID-19 were compared with asymptomatic, seronegative controls. Multivariable logistic regression was used to identify independent symptoms associated with long COVID. Findings All 2,147 participants were contacted and 1,671 (77.8%) completed the questionnaire, including 140 (8.4%) cases and 1,160 controls. At a median of 7.5 (IQR 7.1-7.8) months after infection, 20 cases (14.3%) had ongoing (4/140, 2.9%) or episodic (16/140, 11.4%) symptoms. We identified three clusters of symptoms associated with long COVID, those affecting the sensory (ageusia, anosmia, loss of appetite and blurred vision), neurological (forgetfulness, short-term memory loss and confusion/brain fog) and cardiorespiratory (chest tightness/pain, unusual fatigue, breathlessness after minimal exertion/at rest, palpitations) systems. The sensory cluster had the highest association with being a case (aOR 5.25, 95% CI 3.45-8.01). Dermatological, gynaecological, gastrointestinal or mental health symptoms were not significantly different between cases and controls. Interpretation Most persistent symptoms reported following mild COVID-19 were equally common in cases and controls. While all three clusters identified had a strong association with cases, the sensory cluster had the highest specificity and strength of association, and therefore, most likely to be characteristic of long COVID.

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.

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).

Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection (preprint)

The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, there is concern that immune responses following natural infection may not be sustained and that this may predispose to recurrent infection. We analysed the magnitude and phenotype of the SARS-CoV-2 cellular immune response in 100 donors at six months following primary infection and related this to the profile of antibody level against spike, nucleoprotein and RBD over the previous six months. T-cell immune responses to SARS-CoV-2 were present by ELISPOT or ICS analysis in all donors and are characterised by predominant CD4+ T cell responses with strong IL-2 cytokine expression. Median T-cell responses were 50% higher in donors who had experienced an initial symptomatic infection indicating that the severity of primary infection establishes a set-point for cellular immunity that lasts for at least 6 months. The T-cell responses to both spike and nucleoprotein/membrane proteins were strongly correlated with the peak antibody level against each protein. The rate of decline in antibody level varied between individuals and higher levels of nucleoprotein-specific T cells were associated with preservation of NP-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T-cell responses are retained at six months following infection although the magnitude of this response is related to the clinical features of primary infection.

Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection (preprint)

The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, there is concern that immune responses following natural infection may not be sustained and that this may predispose to recurrent infection. We analysed the magnitude and phenotype of the SARS-CoV-2 cellular immune response in 100 donors at six months following primary infection and related this to the profile of antibody level against spike, nucleoprotein and RBD over the previous six months. T-cell immune responses to SARS-CoV-2 were present by ELISPOT or ICS analysis in all donors and are characterised by predominant CD4+ T cell responses with strong IL-2 cytokine expression. Median T-cell responses were 50% higher in donors who had experienced an initial symptomatic infection indicating that the severity of primary infection establishes a ‘setpoint’ for cellular immunity that lasts for at least 6 months. The T-cell responses to both spike and nucleoprotein/membrane proteins were strongly correlated with the peak antibody level against each protein. The rate of decline in antibody level varied between individuals and higher levels of nucleoprotein-specific T cells were associated with preservation of NP-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T-cell responses are retained at six months following infection although the magnitude of this response is related to the clinical features of primary infection.

Serological surveillance of SARS-CoV-2: trends and humoral response in a cohort of public health workers (preprint)

Background There is considerable debate about the rate of antibody waning after SARS-CoV-2 infection, raising questions around long-term immunity following both natural infection and vaccination. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England. Methods The serosurveillance cohort included office and laboratory-based staff and healthcare workers in 4 sites in England, who were tested monthly for SARS-CoV-2 spike protein and nucleoprotein IgG between 23rd March and 20th August 2020. Antibody levels from 21 days after a positive test were modelled using mixed effects regression models. Findings In total, 2247 individuals were recruited and 2014 (90%) had 3-5 monthly antibody tests. Overall, 272 (12.1%) of individuals had at least one positive/equivocal spike protein IgG result, with the highest proportion in a hospital site (22%), 14% in London and 2.1% in a rural area. Results were similar for nucleoprotein IgG. Following a positive result, 39/587 (6.6%) tested negative for nucleoprotein IgG and 52/515 (10.1%) for spike protein IgG. Nucleoprotein IgG declined by 6.4% per week (95% CI, 5.5-7.4%; half-life, 75 [95% CI, 66-89] days) and spike protein IgG by 5.8% (95% CI, 5.1-6.6%; half-life, 83 [95% CI, 73-96] days). Conclusions Over the study period SARS-CoV-2 seropositivity was 8-10% overall and up to 21% in clinical healthcare workers. In seropositive individuals, nucleoprotein and spike protein IgG antibodies declined with time after infection and 50% are predicted to fall below the positive test threshold after 6 months.

COVID-19 and SARS-CoV-2 Seropositivity in Children of Healthcare Workers in London (preprint)

Background: The COVID-19 pandemic in the UK began in late January 2020 and peaked in mid-April before declining. Children typically develop only very mild symptoms and it remains unclear what role children play in the spread of COVID-19. The aim of this study was to report the prevalence of SARS-CoV-2 antibodies in healthy children of healthcare workers. Methods: Healthy children of healthcare workers, were recruited in London during May 2020. Participants had nose and throat swabs tested for SARS-CoV-2 infection via RT-qPCR and blood serums samples for SARS-CoV-2 immunoglobulin G (IgG) antibodies. Findings: A total of 215 children from 126 families took part and 25(12%) were seropositive for SARS-CoV-2. Children of clinical healthcare workers were significantly more likely to be seropositive 23/133(17%) than those of non-clinical healthcare workers 2/83(2%); p=0.001.In children of parents with confirmed COVID-19, seropositivity was 19/47(40%) compared to 3/44(7%) in children of parents with suspected COVID-19 and 3/124(2%) in children of asymptomatic parents (p<0.001). Overall, 15/83(18%) of symptomatic children were seropositive compared to 10/132(8%) of asymptomatic children (p=0.02). The most commonly reported symptoms were fever 7/25(28%), headache 4/25(16%) and lethargy 5/25(20%). None of the children were hospitalised with COVID-19. Interpretation: The secondary attack rate in children of healthcare workers with confirmed COVID-19 was 40% compared to 2% of children in families with no reported symptoms. One in three seropositive children were asymptomatic.Trial Registration: NCT0434740Funding Statement: This study was funded by the Public Health Agency [COM/5596/20].Declaration of Interests: None disclosed.Ethics Approval Statement: The London (Chelsea) research ethics committee reviewed the study protocol and provided a favourable outcome (Project ID 282617, OREC ID 20/HRA/1731).

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.