The COVID-19 pandemic has led to an unprecedented closure of schools in terms of duration. The option of school closure, SARS-CoV-2 initially being poorly known, was influenced by the epidemiological aspects of the influenza virus. However, school closure is still under debate and seems unsupported by sure evidence of efficacy in the COVID-19 era. The aim of our narrative review is to discuss the available literature on SARS-CoV-2 spread among children and adolescents, in the school setting, trying to explain why children appear less susceptible to severe disease and less involved in viral spreading. We also tried to define the efficacy of school closure, through an overview of the effects of the choices made by the various countries, trying to identify which preventive measures could be effective for a safe reopening. Finally, we focused on the psychological aspects of such a prolonged closure for children and adolescents. SARS-CoV-2, children, COVID-19, influenza, and school were used as key words in our literature research, updated to 29 March 2021. To our knowledge, this is the first review summarizing the whole current knowledge on SARS-CoV-2 spreading among children and adolescents in the school setting, providing a worldwide overview in such a pandemic context.

https://www.mdpi.com/2036-7503/13/2/35/pdf

COVID-19 and School: To Open or Not to Open, That Is the Question. The First Review on Current Knowledge.

Seasonal influenza A (H3N2) virus has been a concern since its first introduction in humans in 1968. Accumulating antigenic changes in viral hemagglutinin (HA), particularly recent cocirculations of multiple HA genetic clades, allow H3N2 virus evade into humans annually. From 2010, the binding of neuraminidase (NA) to sialic acid made the traditional assay for HA inhibition antibodies (Abs) unsuitable for antigenicity characterization. Here, we investigated the serum anti-NA response in a cohort with a seroconversion of microneutralizing (MN) Abs targeting the circulating strain, A/Singapore/INFIMH-16-0019/2016 (H3N2, 3C.2a1)-like, a virus during 2018/2019 flu seasons. We discovered that MN Ab titers show no difference between children and adults. Nevertheless, higher titers of Abs with NA activity inhibition (NI) activity of 129 and seroconversion rate of 68.42% are presented in children aged 7–17 years (n = 19) and 73.47 and 41.17% in adults aged 21–59 years (n = 17), respectively. The MN Abs generated in children display direct correlations with HA- and NA-binding Abs or NI Abs. The NI activity exhibited cross-reactivity to N2 of H3N2 viruses of 2007 and 2013, commonly with 329-N-glycosylation and E344 in N2, a characteristic of earlier 3C.2a H3N2 virus in 2014. The percentage of such viruses pronouncedly decreased and was even replaced by those dominant H3N2 viruses with E344K and 329 non-glycosylation, which have a significantly low activity to the tested antisera. Our findings suggest that NI assay is a testable assay applied in H3N2 infection in children, and the antigenic drift of current N2 should be considered for vaccine selection.

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The Antibody Response Against Neuraminidase in Human Influenza A (H3N2) Virus Infections During 2018/2019 Flu Season: Focusing on the Epitopes of 329-N-Glycosylation and E344 in N2

We performed a retrospective analysis of influenza A and B virus antigen detection data in children in Sichuan Province from January 2019 to December 2021, with the goal of studying the impact of the COVID‐19 pandemic on influenza circulation in children in Sichuan, China. During the pandemic, both the number of specimens and the positive rates of the influenza virus fell dramatically. The positivity for influenza A virus decreased from 22.5% in 2019 to 9.9% in 2020 to 0.2% in 2021 (p < 0.001). The lowest and highest positive rates for the influenza B virus occurred in 2020 and 2021, respectively, with a statistically significant 3‐year comparison (p < 0.001). During the pandemic, the annual positivity remained higher in school‐age than in preschoolers, while there was no difference in the annual positivity between the two gender groups, both consistent with the prepandemic results. During the pandemic, the seasonality of influenza A and B was different from that before the pandemic. In 2019, the epidemic season for influenza A was autumn and winter, while the epidemic season for influenza B was winter and spring. Seasonal changes in influenza A were insignificant after the pandemic, and influenza B became predominant in 2021, with a high prevalence in the autumn. Although influenza activity decreased during the COVID‐19 pandemic, one should be on the lookout for a possible rebound in influenza circulation in the future.

Impact of COVID‐19 pandemic on influenza virus prevalence in children in Sichuan, China

In mainland China, the disease burden of influenza is not yet fully understood. Based on population‐based data, we aimed to estimate incidence rates of medically attended influenza and influenza virus infections in Ningbo City.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/irv.12935

Incidence of medically attended influenza and influenza virus infections confirmed by serology in Ningbo City from 2017–2018 to 2019–2020

Abstract The coexistence of coronavirus disease 2019 (COVID-19) and seasonal influenza epidemics has become a potential threat to human health, particularly in China in the oncoming season. However, with the relaxation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic, the rebound extent of the influenza activities is still poorly understood. In this study, we constructed a susceptible–vaccinated–infectious–recovered–susceptible (SVIRS) model to simulate influenza transmission and calibrated it using influenza surveillance data from 2018 to 2022. We projected the influenza transmission over the next 3 years using the SVIRS model. We observed that, in epidemiological year 2021–2022, the reproduction numbers of influenza in southern and northern China were reduced by 64.0 and 34.5%, respectively, compared with those before the pandemic. The percentage of people susceptible to influenza virus increased by 138.6 and 57.3% in southern and northern China by October 1, 2022, respectively. After relaxing NPIs, the potential accumulation of susceptibility to influenza infection may lead to a large-scale influenza outbreak in the year 2022–2023, the scale of which may be affected by the intensity of the NPIs. And later relaxation of NPIs in the year 2023 would not lead to much larger rebound of influenza activities in the year 2023–2024. To control the influenza epidemic to the prepandemic level after relaxing NPIs, the influenza vaccination rates in southern and northern China should increase to 53.8 and 33.8%, respectively. Vaccination for influenza should be advocated to reduce the potential reemergence of the influenza epidemic in the next few years.

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Quantifying the rebound of influenza epidemics after the adjustment of zero-COVID policy in China

Background In mainland China, seasonal influenza disease burden at community level is unknown. The incidence rate of influenza virus infections in the community is difficult to determine due to the lack of well-defined catchment populations of influenza-like illness surveillance sentinel hospitals. Objectives We established a community-based cohort to estimate incidence of seasonal influenza infections indicated by serology and protection conferred by antibody titers against influenza infections during 2018-2019 influenza season in northern China. Methods We recruited participants in November 2018 and conducted follow-up in May 2019 with collection of sera every survey. Seasonal influenza infections were indicated by a 4-fold or greater increase of hemagglutination inhibition (HI) antibody between paired sera. Results Two hundred and three children 5-17 years of age and 413 adults 18-59 years of age were followed up and provided paired sera. The overall incidence of seasonal influenza infection and incidence of A(H3N2) infection in children (31% and 17%, respectively) were significantly higher than those in adults (21% and 10%, respectively). The incidences of A(H1N1)pdm09 infection in children and adults were both about 10%, while the incidences of B/Victoria and/Yamagata infection in children and adults were from 2% to 4%. HI titers of 1:40 against A(H1N1)pdm09 and A(H3N2) viruses were associated with 63% and 75% protection against infections with the two subtypes, respectively. Conclusions In the community, we identified considerable incidence of seasonal influenza infections. A HI titer of 1:40 could be sufficient to provide 50% protection against influenza A virus infections indicated by serology.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/irv.12805

Incidence of influenza virus infections confirmed by serology in children and adult in a suburb community, northern China, 2018‐2019 influenza season

Vaccination is urgently needed to prevent the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we conducted a randomized, parallel, controlled clinical trial for assessment of the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, aiming to determine an appropriate vaccination interval for high-risk occupational population. Participants were randomly assigned to receive two doses of inactivated SARS-CoV-2 vaccine (4 µg per dose) at an interval of either 14 days, 21 days or 28 days. The primary immunogenicity endpoints were neutralization antibody seroconversion and geometric mean titer (GMT) at 28 days after the second dose. Our results showed that the seroconversion rates (GMT ≥ 16) were all 100% in the three groups and the 0-21 and 0-28 groups elicited significantly higher SARS-CoV-2 neutralizing antibody level. All reported adverse reactions were mild. (Chinese Clinical Trial Registry: ChiCTR2100041705, ChiCTR2100041706)

/pdf/safety-and-immunogenicity-of-inactivated-sars-cov-2-vaccine-3bwvmas5fr.pdf

Ling Liu

Papers

Incidence of influenza virus infections confirmed by serology in children and adult in a suburb community, northern China, 2018‐2019 influenza season

Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccine in High-Risk Occupational Population: a randomized, parallel, controlled clinical trial