Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection.

SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3-11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.

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

The immune response to SARS-CoV-2 is critical in controlling disease, but there is concern that waning immunity may predispose to reinfection. We analyzed the magnitude and phenotype of the SARS-CoV-2-specific T cell response in 100 donors at 6 months following infection. T cell responses were present by ELISPOT and/or intracellular cytokine staining analysis in all donors and characterized by predominant CD4+ T cell responses with strong interleukin (IL)-2 cytokine expression. Median T cell responses were 50% higher in donors who had experienced a symptomatic infection, indicating that the severity of primary infection establishes a 'set point' for cellular immunity. T cell responses to spike and nucleoprotein/membrane proteins were correlated with peak antibody levels. Furthermore, higher levels of nucleoprotein-specific T cells were associated with preservation of nucleoprotein-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 6 months following infection.

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.

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 were investigated to assess the risk of SARS-CoV-2 infection and cumulative incidence 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: Three hundred and twenty-four 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, cumulative incidence was 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 cumulative incidence when the index case was also a staff member (37.52%; 95%CI, 35.39-39.70%). Compared to November 2020, outbreak sizes and cumulative incidence was higher in January 2021, when the Alpha variant predominated. Nationally, SARS-CoV-2 infection rates in < 5 year-olds remained low and followed trends in older age-groups, increasing during December 2020 and declining thereafter. CONCLUSIONS: In this cross-sectional study of COVID-19 outbreaks in nurseries, one in three staff were affected compared to one in thirty children. There was some evidence of increased transmissibility and higher cumulative incidence associated with the Alpha variant, highlighting the importance of maintaining a low level of community infections.

Perceptions of adolescents on the COVID-19 pandemic and returning to school: qualitative questionnaire survey, September 2020, England.

BACKGROUND: Little is known about the views of adolescents returning to secondary school during the current COVID-19 pandemic. METHODS: In September 2020, the UK Health Security Agency (UKHSA), formerly known as 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) of 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 to other students (22.0%; 65/296) or school staff (19.3%; 57/296), or catching the infection themselves (12.5%; 37/296). Students were more likely to maintain 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; 11-14-year-olds) reported not being anxious at all than older students (school years 12-13; 16-18-year-olds) (47/174 [27.0%] vs 3/63 [4.8%]; p = 0.001). Younger students were also less likely to adhere to physical distancing measures and wear face masks. Most students reported positive experiences with SARS-CoV-2 testing in schools, with 92.3% (262/284) agreeing to have another blood test in future visits. CONCLUSIONS: Younger students in secondary schools 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 SARS-CoV-2 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.

Very low risk of monkeypox among staff and students after exposure to a confirmed case in educational settings, England, May to July 2022.

We investigated a secondary school (11-16 year-olds), a primary school (5-11 year-olds), reception year (4-5 year-olds) and a nursery (2-5 year-olds) following confirmed monkeypox in an adult in each educational setting during June and July 2022. MVA-BN vaccine was offered up to 14 days post exposure to 186 children < 12 years and 21 were vaccinated. No secondary cases occurred among at least 340 exposed students and more than 100 exposed staff during the 28-day follow-up period.

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

BACKGROUND: Streptococcus pneumoniae coinfection with influenza results in synergistic lethality, but there are limited data on pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Public Health England conducts invasive pneumococcal disease (IPD) and SARS-CoV-2 surveillance in England. IPD trends during 2000/2001-2019/2020 epidemiological years were analyzed and cases during February-June 2020 linked with laboratory-confirmed SARS-CoV-2 infections. Multivariable logistic regression was used to assess risk factors for death. RESULTS: IPD incidence in 2019/2020 (7.6/100 000; n = 3964) was 30% (IRR, .70; 95% CI, .18-2.67) lower compared with 2018/2019 (10.9/100 000; n = 5666), with large reductions observed across all age groups during March-June 2020. There were 160 886 SARS-CoV-2 and 1137 IPD cases during February-June 2020, including 40 IPD/coronavirus disease 2019 (COVID-19) co-infections (.025% [95% CI, .018-.034] of SARS-CoV-2 infections; 3.5% [2.5-4.8] of IPD cases), 21 with COVID-19 diagnosed 3-27 days after IPD, and 27 who developed COVID-19 ≥28 days after IPD. Case-fatality rates (CFRs) were 62.5 (25/40), 47.6% (10/21), and 33.3% (9/27), respectively (P < .001). In addition to an independent association with increasing age and serotype group, CFR was 7.8-fold (95% CI, 3.8-15.8) higher in those with IPD/COVID-19 coinfection and 3.9-fold (95% CI, 1.4-10.7) higher in patients who developed COVID-19 3-27 days after IPD compared with patients with IPD only. CONCLUSIONS: Large declines in IPD were observed following COVID-19 lockdown. IPD/COVID-19 coinfections were rare but associated with high CFR, mainly in older adults. The rarity, age and serotype distribution of IPD/COVID-19 coinfections do not support wider extension of pneumococcal vaccination.

Secondary Attack Rate and Family Clustering of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children of Healthcare Workers With Confirmed Coronavirus Disease 2019 (COVID-19).

We measured serum SARS-CoV-2 antibodies in 215 children of healthcare workers to estimate secondary attack rates. Twenty-one families had a parent with confirmed COVID-19. There was strong evidence of family clustering (P < .001): 20/21 (95.2%) children were seropositive in 9 families and none of 23 children in 12 other families.

Implementation of preventive measures to prevent COVID-19: a national study of English primary schools in summer 2020.

We examined the feasibility of implementing preventive measures to prevent SARS-CoV-2 transmission across 105 English primary schools in summer 2020 via a survey and interviews with headteachers. High rates of implementation of most recommended measures were noted with the exception of requiring 2 m distance for students, fitting hand sanitizers in classrooms and introducing one-way systems in school corridors. Measures such as regular handwashing and stopping assemblies were considered easy to implement. Majorly challenging measures included distancing between individuals (for students: 51%, N = 99; for staff: 34%; N = 98; for parents: 26%, N = 100), spacing out desks (34%, N = 99), keeping same staff assigned to each student group (33%, N = 97) and staggering break times (25%, N = 99). Rapid implementation was facilitated by staff commitment and communication among stakeholders, but hampered by limitations with guidance received, physical environments, resources, parental adherence and balancing preventive measures with learning. Difficulties with distancing for younger children suggest that smaller bubbles with fewer distancing requirements within these may be a policy option. Schools require further financial, human resource and other support for effective implementation of preventive measures.

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

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