COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) deaths are rare in children and young people (CYP). The high rates of asymptomatic and mild infections complicate assessment of cause of death in CYP. We assessed the cause of death in all CYP with a positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test since the start of the pandemic in England. METHODS AND FINDINGS: CYP aged <20 years who died within 100 days of laboratory-confirmed SARS-CoV-2 infection between 01 March 2020 and 31 December 2021 in England were followed up in detail, using national databases, surveillance questionnaires, post-mortem reports, and clinician interviews. There were 185 deaths during the 22-month follow-up and 81 (43.8%) were due to COVID-19. Compared to non-COVID-19 deaths in CYP with a positive SARS-CoV-2 test, death due to COVID-19 was independently associated with older age (aOR 1.06 95% confidence interval (CI) 1.01 to 1.11, p = 0.02) and underlying comorbidities (aOR 2.52 95% CI 1.27 to 5.01, p = 0.008), after adjusting for age, sex, ethnicity group, and underlying conditions, with a shorter interval between SARS-CoV-2 testing and death. Half the COVID-19 deaths (41/81, 50.6%) occurred within 7 days of confirmation of SARS-CoV-2 infection and 91% (74/81) within 30 days. Of the COVID-19 deaths, 61 (75.3%) had an underlying condition, especially severe neurodisability (n = 27) and immunocompromising conditions (n = 12). Over the 22-month surveillance period, SARS-CoV-2 was responsible for 1.2% (81/6,790) of all deaths in CYP aged <20 years, with an infection fatality rate of 0.70/100,000 SARS-CoV-2 infections in this age group estimated through real-time, nowcasting modelling, and a mortality rate of 0.61/100,000. Limitations include possible under-ascertainment of deaths in CYP who were not tested for SARS-CoV-2 and lack of direct access to clinical data for hospitalised CYP. CONCLUSIONS: COVID-19 deaths remain extremely rare in CYP, with most fatalities occurring within 30 days of infection and in children with specific underlying conditions.

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.

Acute and Persistent Symptoms in Children With Polymerase Chain Reaction (PCR)-Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Compared With Test-Negative Children in England: Active, Prospective, National Surveillance.

BACKGROUND: Most children recover quickly after coronavirus disease 2019 (COVID-19), but some may have ongoing symptoms. Follow-up studies have been limited by small sample sizes and lack of appropriate controls. METHODS: We used national testing data to identify children aged 2-16 years with a SARS-CoV-2 PCR test during 1-7 January 2021 and randomly selected 1500 PCR-positive cases and 1500 matched PCR-negative controls. Parents were asked to complete a questionnaire about the acute illness and prespecified neurological, dermatological, sensory, respiratory, cardiovascular, gastrointestinal, mental health (including emotional and behavioral well-being), and other symptoms experienced ≥5 times at 1 month after the PCR test. RESULTS: Overall, 35.0% (859/2456) completed the questionnaire, including 38.0% (472/1242) of cases and 32% (387/1214) of controls, of whom 68% (320/472) and 40% (154/387) were symptomatic, respectively. The most prevalent acute symptoms were cough (249/859, 29.0%), fever (236/859, 27.5%), headache (236/859, 27.4%), and fatigue (231/859, 26.9%). One month later, 21/320 (6.7%) of symptomatic cases and 6/154 (4.2%) of symptomatic controls (P = .24) experienced ongoing symptoms. Of the 65 ongoing symptoms solicited, 3 clusters were significantly (P < .05) more common, albeit at low prevalence, among symptomatic cases (3-7%) than symptomatic controls (0-3%): neurological, sensory, and emotional and behavioral well-being. Mental health symptoms were reported by all groups but more frequently among symptomatic cases than symptomatic controls or asymptomatic children. CONCLUSIONS: Children with symptomatic COVID-19 had a slightly higher prevalence of ongoing symptoms than symptomatic controls, and not as high as previously reported. Healthcare resources should be prioritized to support the mental health of children.

Increased Incidence of Invasive Pneumococcal Disease among Children after COVID-19 Pandemic, England.

During July-December 2021, after COVID-19 restrictions were removed in England, invasive pneumococcal disease incidence in children <15 years of age was higher (1.96/100,000 children) than during the same period in 2020 (0.7/100,000 children) and in prepandemic years 2017-2019 (1.43/100,000 children). Childhood vaccine coverage should be maintained to protect the population.

mRNA or ChAd0x1 COVID-19 Vaccination of Adolescents Induces Robust Antibody and Cellular Responses With Continued Recognition of Omicron Following mRNA-1273.

Children and adolescents generally experience mild COVID-19. However, those with underlying physical health conditions are at a significantly increased risk of severe disease. Here, we present a comprehensive analysis of antibody and cellular responses in adolescents with severe neuro-disabilities who received COVID-19 vaccination with either ChAdOx1 (n=6) or an mRNA vaccine (mRNA-1273, n=8, BNT162b2, n=1). Strong immune responses were observed after vaccination and antibody levels and neutralisation titres were both higher after two doses. Both measures were also higher after mRNA vaccination and were further enhanced by prior natural infection where one vaccine dose was sufficient to generate peak antibody response. Robust T-cell responses were generated after dual vaccination and were also higher following mRNA vaccination. Early T-cells were characterised by a dominant effector-memory CD4+ T-cell population with a type-1 cytokine signature with additional production of IL-10. Antibody levels were well-maintained for at least 3 months after vaccination and 3 of 4 donors showed measurable neutralisation titres against the Omicron variant. T-cell responses also remained robust, with generation of a central/stem cell memory pool and showed strong reactivity against Omicron spike. These data demonstrate that COVID-19 vaccines display strong immunogenicity in adolescents and that dual vaccination, or single vaccination following prior infection, generate higher immune responses than seen after natural infection and develop activity against Omicron. Initial evidence suggests that mRNA vaccination elicits stronger immune responses than adenoviral delivery, although the latter is also higher than seen in adult populations. COVID-19 vaccines are therefore highly immunogenic in high-risk adolescents and dual vaccination might be able to provide relative protection against the Omicron variant that is currently globally dominant.

Severe Acute Respiratory Syndrome Coronavirus 2 Infections in Primary School Age Children After Partial Reopening of Schools in England.

In England, the easing of national lockdown in response to the coronavirus disease 2019 pandemic included the reopening of some primary school years on June 1, 2020. National surveillance did not identify any increase in the year groups attending school. Most children had a severe acute respiratory syndrome coronavirus 2 positive household contact. Hospitalizations for coronavirus disease 2019 were rare, but 2.7% (7/259) had persistent symptoms 1 month later.

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.

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.

Increased risk of SARS-CoV-2 infection in staff working across different care homes: enhanced CoVID-19 outbreak investigations in London care Homes.

BACKGROUND: Care homes have been disproportionately affected by the COVID-19 pandemic and continue to suffer large outbreaks even when community infection rates are declining, thus representing important pockets of transmission. We assessed occupational risk factors for SARS-CoV-2 infection among staff in six care homes experiencing a COVID-19 outbreak during the peak of the pandemic in London, England. METHODS: Care home staff were tested for SARS-COV-2 infection by RT-PCR and asked to report any symptoms, their contact with residents and if they worked in different care homes. Whole genome sequencing (WGS) was performed on RT-PCR positive samples. RESULTS: In total, 53 (21%) of 254 staff were SARS-CoV-2 positive but only 12/53 (23%) were symptomatic. Among staff working in a single care home, SARS-CoV-2 positivity was 15% (2/13), 16% (7/45) and 18% (30/169) in those reporting no, occasional and regular contact with residents. In contrast, staff working across different care homes (14/27, 52%) had a 3.0-fold (95% CI, 1.9-4.8; P<0.001) higher risk of SARS-CoV-2 positivity than staff working in single care homes (39/227, 17%). WGS identified SARS-CoV-2 clusters involving staff only, including some that included staff working across different care homes. CONCLUSIONS: SARS-CoV-2 positivity was significantly higher among staff working across different care homes than those who were working in the same care home. We found local clusters of SARS-CoV-2 infection between staff only, including those with minimal resident contact. Infection control should be extended for all contact, including those between staff, whilst on care home premises.

Investigation of SARS-CoV-2 outbreaks in six care homes in London, April 2020.

BACKGROUND: Care homes are experiencing large outbreaks of COVID-19 associated with high case-fatality rates. We conducted detailed investigations in six London care homes reporting suspected COVID-19 outbreaks during April 2020. METHODS: Residents and staff had nasal swabs 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, 105/264 (39.8%) residents were SARS CoV-2 positive, including 28 (26.7%) symptomatic, 10 (9.5%) post-symptomatic, 21 (20.0%) pre-symptomatic and 46 (43.8%) who remained asymptomatic. Case-fatality at 14-day follow-up was highest among symptomatic SARS-CoV-2 positive residents (10/28, 35.7%) compared to asymptomatic (2/46, 4.3%), post-symptomatic (2/10, 20.0%) or pre-symptomatic (3/21,14.3%) residents. Among staff, 53/254 (20.9%) were SARS-CoV-2 positive and 26/53 (49.1%) remained asymptomatic. RT-PCR cycle-thresholds and live-virus recovery were similar between symptomatic/asymptomatic residents/staff. Higher RT-PCR cycle threshold values (lower virus load) samples were associated with exponentially decreasing ability to recover infectious virus (P<0.001). WGS identified multiple (up to 9) separate introductions of different SARS-CoV-2 strains into individual care homes. INTERPRETATION: A high prevalence of SARS-CoV-2 positivity was found in care homes residents and staff, half of whom were asymptomatic and potential reservoirs for on-going transmission. A third of symptomatic SARS-CoV-2 residents died within 14 days. Symptom-based screening alone is not sufficient for outbreak control. FUNDING: None.