Although the COVID-19-related symptoms and prognosis are better in children than in adults (Ludvigsson, 2020), COVID-19 has an unneglectable impact on children. The major SARS-CoV-2 variants evolved from pre-Alpha, Alpha, and Delta, to Omicron (Mattiuzzi and Lippi, 2022). The hospital admission rate in children with COVID-19 varies widely and is influenced by the evolving SARS-CoV-2 dominant variants, healthcare system availability, and different age groups and immunization status. At the beginning of the COVID-19 pandemic in 2020, multinational studies from Europe and China revealed that 51–62% of children required hospital admission, 7–8% required intensive care unit (ICU) admission, and 4% required mechanical ventilation (Götzinger et al., 2020; Bhuiyan et al., 2021). Clinical severity in children has considerably changed over time, after the initiation of immunization programs and evolution of SARS-CoV-2 variants. By 2021, most children had mild symptoms (58%) or were asymptomatic (36%) (Say et al., 2021). Following the extension of immunization to infants aged >6 months, hospitalization rates declined to 0.02–0.2% in fully vaccinated children (González et al., 2022; Tan et al., 2022). Thereafter, hospitalization rates stabilized and remain low to date.

Children who recovered from COVID-19 generated a robust immune response and developed protective immunity. A meta-analysis concluded an 87% reduction in SARS-CoV-2 reinfection in those previously infected compared to those who were never infected (Deng et al., 2022). Moreover, even though children and adolescents were either asymptomatic or experienced only mild symptoms during their first SARS-CoV-2 infections, all participants demonstrated seropositive SARS-CoV-2-specific antibodies. Although the antibody titer in these children was low compared to that in adults, 92% still exhibited virus-neutralizing activity, which may protect them from reinfections (Szépfalusi et al., 2021). Interestingly, SARS-CoV-2 antibody titers did not differ between asymptomatic and symptomatic children (Maier et al., 2022). In addition to humoral immunity, IgA antibodies play a role in mucosal immunity by eliminating viral replication and reducing the risk of reinfection (Zohar and Alter, 2020). Asymptomatic infections are more common in children (Yasuhara et al., 2020), and the trend of receiving SARS-CoV-2 testing is gradually decreasing (Park et al., 2023). As of August 2022, a national commercial laboratory seroprevalence study demonstrated that approximately 86% of children and adolescents in the US had serologic evidence of previous SARS-CoV-2 infection (Son et al., 2023).

The risk and picture of SARS-CoV-2 reinfection are changing, and the emergence of new variants can partially evade immunity from previous infection or vaccination (Milne et al., 2021). The risk of reinfection increases with age in infants, children, and adolescents (Mensah et al., 2022; Medić et al., 2023). A previous study reported a J-shaped curve of antibody titers with respect to age after the first SARS-CoV-2 infection. Antibody titers were lowest among adolescents and young adults, higher in younger children, and highest among older adults (Maier et al., 2022). The J-shaped distribution of antibodies may partly explain the high risk of reinfection in adolescents.

Fortunately, the risk of symptomatic COVID-19 reinfection was lower in seropositive children, whose relative risk of being symptomatic was reduced to 36–51% (Kubale et al., 2022). Although moderate and severe cases could still occur in reinfection, there was no difference in severity between first and second infections (Kubale et al., 2022). Therefore, recurrent infection was not a risk factor for severe COVID-19.

During the first wave of the COVID-19 pandemic, public health measures were strictly applied, including social distancing, increased awareness of wearing masks, reinforced hand hygiene, reduced contact between children, maintaining ventilation, containment, curfew, and closure of schools and daycare centers. Implementation of public health measures led to abrupt declines in human respiratory syncytial virus (RSV) and influenza infections worldwide in 2020 and 2021 due to a reduction in the circulation of respiratory viruses, with a reported reduction in infection rates of up to 98–99% (Baker et al., 2020; Feng et al., 2021; Stamm et al., 2021; Stera et al., 2021; van Summeren et al., 2021; Yeoh et al., 2021; Binns et al., 2022; Zhang et al., 2023). Declines in RSV and influenza and reduced transmission of other respiratory viral pathogens, including common human coronavirus, parainfluenza viruses, human metapneumovirus, adenovirus, rhinovirus, and enterovirus have been observed in the US (Olsen et al., 2021; Rankin et al., 2023).

Bruggink et al. also reported a significant reduction in enterovirus infections during the 2020 early COVID-19 pandemic period in Australia. Mitigation measures resulted in an 84.2% reduction in enterovirus specimen positivity rate compared to previous decades, as the number of tested specimens did not differ appreciably in 2020 from that during 2010–2019 (Bruggink et al., 2021).

The incidence of invasive diseases due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis in early 2020 was significantly reduced in 26 countries (Brueggemann et al., 2021). Furthermore, the number of invasive pneumococcal disease (IPD) cases in children in Spain in 2020 decreased by 65% compared to 2018–2019 (Ciruela et al., 2022). Similarly, pneumococcal infections among children in China showed a decreasing trend during the 2020 early COVID-19 pandemic period (Li et al., 2022). Interestingly, studies from Israel, France, and Belgium reported that even though pneumococcal infection reduced strongly in 2020 and early 2021, pneumococcal carriage in young children declined only slightly during the pandemic (Willen et al., 2021; Danino et al., 2022; Rybak et al., 2022). Therefore, the major explanation for the reduced pneumococcal disease was the full suppression of co-pathogens that can lead to secondary pneumococcal infections, including RSV, influenza viruses, and human metapneumovirus, instead of the decreased number of pneumococcal carriages (Willen et al., 2021; Danino et al., 2022; Rybak et al., 2022). A reduction in Haemophilus influenzae infections in children has also been reported in China. The positivity rates of H. influenzae infection in children with respiratory tract infections in 2020 (6.21%) and 2021 (7.37%) were lower than those in 2018 (11.28%) and 2019 (10.16%) (Zhou et al., 2023).

An epidemiological and observational study in Northern Italy revealed a reduction in the prevalence of chickenpox, scarlet fever, pertussis, mumps, rubella, and measles in children (Belingheri et al., 2021). A report from the European Centre for Disease Prevention and Control also demonstrated that the number of measles cases declined in European Union countries and the United Kingdom in 2020 (Nicolay et al., 2020). Moreover, data from the China Disease Prevention and Control Information System showed a significant decrease in the number of varicella, measles, and rubella infections in 2020 (Wu et al., 2020).

Furthermore, the annual number of community-acquired infectious diseases among children in France decreased by one-third in 2020 compared to 2018 and 2019, including scarlet fever, acute tonsillopharyngitis, enteroviral infections, acute bronchiolitis, and gastroenteritis (Cohen et al., 2022). The incidence of acute otitis media, acute bronchiolitis, and croup also decreased among children in the US during the 2020 COVID-19 pandemic (Kaur et al., 2021).

The volume of pediatric emergency department visits and admissions also declined throughout the COVID-19 pandemic (DeLaroche et al., 2021; Moynihan et al., 2021; Miron et al., 2022b). A comprehensive systematic review further documented a 37% reduction in overall healthcare services, encompassing a 42% and 28% decrease in visits and admissions, respectively (Moynihan et al., 2021).

Country-based mitigation measures in Taiwan successfully delayed the COVID-19 epidemic until May 2022. Implementing mitigation measures also contributed to a decrease in the burden of other infectious diseases to hospitals. A report from Taiwan suggested an approximately 50% reduction in pediatric patient volume per hour at the emergency department between February 2020 and January 2021 compared with the pre-COVID-19 period (February 2019 to January 2020). The most obvious drop was noted for infectious diseases, especially influenza and enterovirus infections (Huang et al., 2022). The general population of Taiwan is approximately 23 million. According to the Taiwan CDC report ( Figure 1 ), there was a 95–98% reduction in the rate of influenza-related critical illnesses in 2021–2022 compared to 2013–2019. The incidence of IPD, pertussis, enterovirus-related critical illness, measles, mumps, and rubella also decreased significantly during the COVID-19 pandemic. However, the tuberculosis incidence has declined annually since 2013 with a steady rate of de-escalation of 1,000 cases every two years, from 11,528 cases in 2013 to 6,387 in 2022; this change rate did not differ before and after the COVID-19 pandemic. Conversely, there was no decline in Legionella pneumonia infection rates, which steadily increased over the past decade, from 115 cases in 2013 to 382 in 2022 (Taiwan Centers for Disease).

Immunity debt leading to off-season resurgence of respiratory viral infections in several countries has been observed since 2021, after the wide-scale implementation of SARS-CoV-2 vaccination campaigns and easing of restrictive measures. Infants and children spent more time in daycare centers and schools than they did during the initial COVID-19 period; therefore, young children had a higher risk of infection. Previously RSV infections had a seasonal peak; however, the impact of COVID-19 mitigation measures contributed to “off-season” RSV bronchiolitis resurgence in France, England, and Israel (Casalegno et al., 2021; Delestrain et al., 2021; Rybak et al., 2021; Weinberger Opek et al., 2021; Billard and Bont, 2023). Furthermore, an alternating “see-sawing” pattern of COVID-19 and RSV infections in children has been observed in France, Italy, the US, and Australia (Agha and Avner, 2021; Delestrain et al., 2021; Eden et al., 2022; Rabbone et al., 2022). Strict restrictions during the COVID-19 outbreak periods flattened the RSV bronchiolitis epidemic; in contrast, unrestrained regulations after the cooldown of COVID-19 led to a resurgence of RSV infections ( Figure 2 ).

Other than the “off-season” and “see-sawing” features, “upsurge” pattern occurs as well in respiratory infectious diseases during the COVID-19 pandemic ( Figure 2 ). Several countries reported that RSV infection reached its highest peak after dismissal of public health mitigation policies. In Japan, the largest increase in RSV bronchiolitis cases in children began in 2021. The cumulative number of RSV infections rose from 570 in 2020 to 10,327 in the early-to-middle 2021 (Ujiie et al., 2021). In New Zealand, a rapid increase in RSV bronchiolitis in children aged 0–4 years was observed after relaxation of the strict border closure policy in April 2021. The RSV incidence was three times higher than in 2015–2019, which contributed to more hospitalizations and ICU admissions due to RSV in this age group (Hatter et al., 2021). The RSV upsurge in Australia occurred from late September to November 2020, when RSV infections exceeded the median 2012–2019 seasonal peak. Considering the prior waning of population immunity to RSV from 2019 to mid-2020, there were more RSV-naïve older children. Thus, the median patient age in 2020 was 18.4 months, which was significantly higher than the upper range between 2012–2019 (7.3–12.5 months) (Foley et al., 2021). Because of the delayed first RSV infection during the COVID-19 pandemic, RSV-related hospital admissions were higher among children aged 24–59 months compared to younger ages (Nygaard et al., 2023; Rao et al., 2023a).

A national population register in Norway revealed a surge in respiratory tract infection admissions from September to October 2021 among all children aged 0–5 years, which exceeded the numbers usually observed at the typical season peak in January. The major causes were RSV-related and lower respiratory tract infection-related admissions. Conversely, the number of influenza-related admissions remained low during this period (Methi et al., 2021). A study in Italy demonstrated an extensive epidemic of pediatric acute respiratory infections from June to October 2021. Compared to October 2019, RSV, parainfluenza, rhinoviruses/enteroviruses, metapneumoviruses, common coronaviruses, and adenoviruses were more frequently isolated from specimens in October 2021 (Mattana et al., 2022). It is worth noting that coinfections with two and three viruses were found in approximately 30% and 7% of all positive cases, respectively. This finding highlights the increasing circulation of these viruses by 2021 (Mattana et al., 2022).

The “see-sawing” and “upsurging” patterns were also observed for influenza infections. Following two years of decline in influenza virus circulation during the early COVID-19 pandemic, influenza infection rates increased in 2022, coinciding with a decrease in SARS-CoV-2 infections (Miron et al., 2022a; Lei et al., 2023; Rao et al., 2023b). Relaxation of non-pharmacological interventions subsequently resulted in a significant accumulation of influenza infections, leading to a widespread influenza outbreak.

The upsurge in infections after the COVID-19 pandemic also occurred in children with IPD. In a national enhanced surveillance in England, the children’s IPD incidence declined by 50% in 2020 but increased in 2021 after lifting COVID-19 social restrictions. Additionally, the 2021 children’s IPD incidence (1.96/100,000) was higher than that during the same period in pre-pandemic years 2017–2019 (1.43/100,000) (Bertran et al., 2022). A study in Germany also indicated that the children’s IPD incidence exceeded seasonal levels in 2021, concurrent with the dismissal of non-pharmaceutical interventions intended to lower the SARS-CoV-2 transmission. From April to June 2021, IPD among children exceeded 9% of the average monthly values for 2015–2019 (Perniciaro et al., 2022). Although large-scale IPD has not been reported in other countries, it is still necessary to pay attention to the surge after loosening public mitigation restrictions.

A similar upsurge was observed for enterovirus infections. Since there was a very low prevalence of enterovirus infection after hygiene reinforcement in France in 2020, reduced immune stimulation and greater susceptibility to enterovirus led to a large-scale outbreak of hand, foot, and mouth diseases (HFMDs) in children. A total of 3,403 cases were reported from January to September 2021, which was 47% higher than during the same period in 2018–2019 (Mirand et al., 2021). Likewise, after easing COVID-19 mitigation measures, enterovirus cases re-emerged in 18 European countries between January and October 2021. Although the number of samples tested monthly remained unchanged, the proportion of samples identified as enteroviruses increased from 2.5% in January to 8.2% in September. The positivity rate of enterovirus-D68 also increased from 0.2% in January to 14% in September 2021 (Benschop et al., 2021). Furthermore, soon after dismissal of non-pharmaceutical interventions in 2021, Brazil’s Information System for Notifiable Diseases reported a large-scale outbreak of HFMDs that was exclusively associated with the re-emergence of the Coxsackievirus A6 sublineage (Carmona et al., 2022). These outbreaks could be attributed to immunity debt to enteroviruses during the COVID-19 pandemic.