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As of July 2021, over 3 billion doses of a COVID-19 vaccines have been administered globally, and there are now 19 COVID-19 vaccines approved for use in at least one country. Several of these have been shown to be highly effective both in clinical trials and real-world observational studies, some of which have included special populations of interest. A small number of countries have approved a COVID-19 vaccine for use in adolescents or children. These are laudable achievements, but the global vaccination effort has been challenged by inequitable distribution of vaccines predominantly to high income countries, with only 0.9% of people in low-income countries having received at least one dose of a COVID-19 vaccine. Addressing this inequity is of critical importance and will result in better control of SARS-CoV-2 globally. Other challenges include: the reduced protection from COVID-19 vaccines against some strains of SARS-CoV-2, necessitating the development of variant specific vaccines; and uncertainties around the duration of protection from vaccine-induced immunity.

In 2020, school and early childhood educational centre (ECEC) closures affected over 1.5 billion school‐aged children globally as part of the COVID‐19 pandemic response. Attendance at school and access to ECEC is critical to a child's learning, well‐being and health. School closures increase inequities by disproportionately affecting vulnerable children. Here, we summarise the role of children and adolescents in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) transmission and that of schools and ECECs in community transmission and describe the Australian experience. In Australia, most SARS‐CoV‐2 cases in schools were solitary (77% in NSW and 67% in Victoria); of those that did progress to an outbreak, >90% involved fewer than 10 cases. Australian and global experience has demonstrated that SARS‐CoV‐2 is predominantly introduced into schools and ECECs during periods of heightened community transmission. Implementation of public health mitigation strategies, including effective testing, tracing and isolation of contacts, means schools and ECECs can be safe, not drivers of transmission. Schools and ECEC are essential services and so they should be prioritised to stay open for face‐to‐face learning. This is particularly critical as we continue to manage the next phase of the COVID‐19 pandemic.

Summary Background School closures have occurred globally during the COVID-19 pandemic. However, empiric data on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and in educational settings are scarce. In Australia, most schools have remained open during the first epidemic wave, albeit with reduced student physical attendance at the epidemic peak. We examined SARS-CoV-2 transmission among children and staff in schools and early childhood education and care (ECEC) settings in the Australian state of New South Wales (NSW). Methods Laboratory-confirmed paediatric (aged ≤18 years) and adult COVID-19 cases who attended a school or ECEC setting while considered infectious (defined as 24 h before symptom onset based on national guidelines during the study period) in NSW from Jan 25 to April 10, 2020, were investigated for onward transmission. All identified school and ECEC settings close contacts were required to home quarantine for 14 days, and were monitored and offered SARS-CoV-2 nucleic acid testing if symptomatic. Enhanced investigations in selected educational settings included nucleic acid testing and SARS-CoV-2 antibody testing in symptomatic and asymptomatic contacts. Secondary attack rates were calculated and compared with state-wide COVID-19 rates. Findings 15 schools and ten ECEC settings had children (n=12) or adults (n=15) attend while infectious, with 1448 contacts monitored. Of these, 633 (43·7%) of 1448 had nucleic acid testing, or antibody testing, or both, with 18 secondary cases identified (attack rate 1·2%). Five secondary cases (three children; two adults) were identified (attack rate 0·5%; 5/914) in three schools. No secondary transmission occurred in nine of ten ECEC settings among 497 contacts. However, one outbreak in an ECEC setting involved transmission to six adults and seven children (attack rate 35·1%; 13/37). Across all settings, five (28·0%) of 18 secondary infections were asymptomatic (three infants [all aged 1 year], one adolescent [age 15 years], and one adult). Interpretation SARS-CoV-2 transmission rates were low in NSW educational settings during the first COVID-19 epidemic wave, consistent with mild infrequent disease in the 1·8 million child population. With effective case-contact testing and epidemic management strategies and associated small numbers of attendances while infected, children and teachers did not contribute significantly to COVID-19 transmission via attendance in educational settings. These findings could be used to inform modelling and public health policy regarding school closures during the COVID-19 pandemic. Funding NSW Government Department of Health.

Despite severe outbreaks of COVID-19 among colleges and universities across the USA during the Fall 2020 semester, the majority of institutions did not routinely test students. While high-frequency repeated testing is considered the most effective strategy for disease mitigation, most institutions do not have the necessary infrastructure or funding for implementation. Therefore, alternative strategies for testing the student population are needed. Our study detailed the implementation and results of testing strategies to mitigate SARS-CoV-2 spread on a university campus, and we aimed to assess the relative effectiveness of the different testing strategies.For this retrospective cohort study, we included 6273 on-campus students arriving to a large public university in the rural USA (Clemson, SC, USA) for in-person instruction in the Fall 2020 semester (Sept 21 to Nov 25). Individuals arriving after Sept 23, those who tested positive for SARS-CoV-2 before Aug 19, and student athletes and band members were not included in this study. We implemented two testing strategies to mitigate SARS-CoV-2 spread during this period: a novel surveillance-based informative testing (SBIT) strategy, consisting of random surveillance testing to identify outbreaks in residence hall buildings or floors and target them for follow-up testing (Sept 23 to Oct 5); followed by a repeated weekly surveillance testing (Oct 6 to Nov 22). Relative changes in estimated weekly prevalence were examined. We developed SARS-CoV-2 transmission models to compare the relative effectiveness of weekly testing (900 daily surveillance tests), SBIT (450 daily surveillance tests), random surveillance testing (450 daily surveillance tests), and voluntary testing (0 daily surveillance tests) on disease mitigation. Model parameters were based on our empirical surveillance data in conjunction with published sources.SBIT was implemented from Sept 23 to Oct 5, and identified outbreaks in eight residence hall buildings and 45 residence hall floors. Targeted testing of residence halls was 2·03 times more likely to detect a positive case than random testing (95% CI 1·67-2·46). Weekly prevalence was reduced from a peak of 8·7% to 5·6% during this 2-week period, a relative reduction of 36% (95% CI 27-44). Prevalence continued to decrease after implementation of weekly testing, reaching 0·8% at the end of in-person instruction (week 9). SARS-CoV-2 transmission models concluded that, in the absence of SBIT (ie, voluntary testing only), the total number of COVID-19 cases would have increased by 154% throughout the semester. Compared with SBIT, random surveillance testing alone would have resulted in a 24% increase in COVID-19 cases. Implementation of weekly testing at the start of the semester would have resulted in 36% fewer COVID-19 cases throughout the semester compared with SBIT, but it would require twice the number of daily tests.It is imperative that institutions rigorously test students during the 2021 academic year. When high-frequency testing (eg, weekly) is not possible, SBIT is an effective strategy to mitigate disease spread among the student population that can be feasibly implemented across colleges and universities.Clemson University, USA.

SUMMARYChildren infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV- 2-specific naïve T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. More naïve interferon-activated CD4+ T cells were recruited into the memory compartment and recovery was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.HIGHLIGHTSChildren have diverse polyclonal SARS-CoV-2-specific naïve T cellsAdults have clonally expanded exhausted SARS-CoV-2-specific memory T cellsInterferon-activated naïve T cells differentiate into memory T cells in adults but not childrenAdults but not children develop robust memory T cell responses to SARS-CoV-2

The global disruption of the COVID-19 pandemic has impacted the life of every child either directly or indirectly. This review explores the pathophysiology, immune response, clinical presentation and treatment of COVID-19 in children, summarising the most up-to-date data including recent developments regarding variants of concern. The acute infection with SARS-CoV-2 is generally mild in children, whilst the post-infectious manifestations, including paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and 'long COVID' in children, are more complex. Given that most research on COVID-19 has focused on adult cohorts and that clinical manifestations, treatment availability and impacts differ markedly in children, research that specifically examines COVID-19 in children needs to be prioritised.

There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 - the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.

There are currently around 200 SARS-CoV-2 candidate vaccines in preclinical and clinical trials throughout the world. The various candidates employ a range of vaccine strategies including some novel approaches. Currently, the goal is to prove that they are safe and immunogenic in humans (phase 1/2 studies) with several now advancing into phase 2 and 3 trials to demonstrate efficacy and gather comprehensive data on safety. It is highly likely that many vaccines will be shown to stimulate antibody and T cell responses in healthy individuals and have an acceptable safety profile, but the key will be to confirm that they protect against COVID-19. There is much hope that SARS-CoV-2 vaccines will be rolled out to the entire world to contain the pandemic and avert its most damaging impacts. However, in all likelihood this will initially require a targeted approach toward key vulnerable groups. Collaborative efforts are underway to ensure manufacturing can occur at the unprecedented scale and speed required to immunize billions of people. Ensuring deployment also occurs equitably across the globe will be critical. Careful evaluation and ongoing surveillance for safety will be required to address theoretical concerns regarding immune enhancement seen in previous contexts. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. We provide details of some of the frontrunner vaccines and discuss potential issues including adverse effects, scale-up and delivery.