The coronavirus disease 2019 (COVID‑19) pandemic has fundamentally altered the epidemiology, clinical presentation, and management of infectious diseases in children worldwide. The implementation of unprecedented public health measures, including school closures, mask mandates, and social distancing, not only curtailed the transmission of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) but also dramatically shifted the prevalence and seasonal patterns of other common pediatric infections. As we now survey the post‑restriction landscape, a complex picture has emerged, revealing both immediate and delayed effects on pediatric infectious disease trends. This editorial reviews the evolving patterns of childhood infections before, during, and after the COVID‑19 pandemic and highlights substantial changes in disease prevalence, seasonality, and severity that pose new challenges for healthcare providers.
1. Direct impact of COVID-19 on children: an evolving narrative
The impact of SARS‑CoV‑2 infection on pediatric populations has changed markedly over the course of the pandemic. Early data from 2020 suggested that children were less susceptible to infection and generally experienced milder disease than adults. Multinational studies from Europe and China reported that 51%–62% of infected children required hospitalization, 7%–8% needed intensive care, and 4% required mechanical ventilation. Subsequently, the clinical picture evolved in tandem with emerging variants and vaccination programs. By 2021, most children (58%) exhibited only mild symptoms, and 36% remained completely asymptomatic. Following the extension of vaccination to children older than 6 months, hospitalization rates among fully immunized children fell to 0.02%–0.2% [
1,
2]. This progressive decrease in severity coincided with expanding population immunity and the appearance of new SARS‑CoV‑2 variants.
The emergence of more transmissible variants, particularly Delta and Omicron, significantly altered the epidemiological landscape for children. Global prevalence data indicated rising SARS-CoV-2 infection rates among children and adolescents, partly driven by increased adult vaccination coverage and the circulation of these highly transmissible variants [
3]. The Omicron variant, in particular, displayed a distinctive pattern in pediatric populations—while it led to a substantial increase in infections and hospital admissions among children, the severity of disease was generally less pronounced than with previous variants. In the United Kingdom, during the Omicron surge from December 2021 to January 2022, infants under 1 year of age accounted for 42.2% of pediatric hospital admissions, marking a significant increase compared to earlier pandemic periods. However, data from Scotland, the United States, South Africa, and England revealed lower hospitalization rates with Omicron compared to Delta infections. A retrospective cohort study in the United States involving 577,938 patients found that the hospitalization risk during the Omicron period was approximately one-third of that observed during the Delta period across all pediatric age groups [
4] (
Table 1).
2. The suppression effect: changes in infectious disease patterns during COVID-19 restrictions
One of the most notable consequences of COVID-19 mitigation strategies was the dramatic reduction in the incidence of common childhood infections. Stringent non-pharmaceutical interventions implemented globally profoundly affected the transmission dynamics of nearly all infectious pathogens affecting children.
Invasive pneumococcal disease (IPD) exemplifies this clearly. In early 2020, IPD cases substantially declined across 26 countries. Spain experienced a 65% decrease in pediatric IPD cases in 2020 compared to the period 2018–2019. Similarly, China reported reductions in pediatric pneumococcal infections during the early pandemic period. This trend extended beyond pneumococcal disease to numerous other infections. In France, the annual incidence of community-acquired infectious diseases among children fell by one-third in 2020 relative to previous years, affecting conditions including scarlet fever, acute tonsillopharyngitis, enteroviral infections, acute bronchiolitis, and gastroenteritis [
1].
Healthcare utilization patterns reflected these epidemiological changes, with pediatric emergency department visits and hospital admissions significantly declining during the pandemic. Systematic reviews documented a 37% overall reduction in healthcare service utilization, including a 42% decrease in visits and a 28% decrease in admissions [
1]. These reductions paralleled the decreased circulation of common pediatric pathogens.
The landscape for viral respiratory infections was particularly altered. Data from a large metropolitan children’s hospital indicated that before 2020, there was a median of 1,080 respiratory pathogen tests performed weekly, with positivity rates between 3.7%–4.1%. In 2020, this sharply decreased to 486 tests per week with a positivity rate of just 1.74% [
5]. The suppression of respiratory viruses such as respiratory syncytial virus (RSV) and influenza was unprecedented, with seasonal peaks nearly eliminated during periods of the strictest restrictions.
3. The rebound effect: post-restriction resurgence patterns
As COVID-19 restrictions were gradually lifted, particularly following extensive vaccination campaigns, a remarkable resurgence of previously suppressed infections became evident. This rebound has manifested in several distinct patterns that challenge the conventional understanding of seasonal infectious disease epidemiology.
Researchers have identified three predominant resurgence patterns for respiratory viral infections, particularly notable with RSV:
“Off-season” pattern: This pattern involved traditionally seasonal infections emerging at atypical times of the year. For instance, countries including France, England, and Israel reported surges of RSV bronchiolitis during non-traditional seasons [
1,
2]. This temporal shift disrupted established clinical expectations and resource allocation models.
“See-sawing” pattern: An alternating relationship between COVID-19 and other respiratory infections became apparent. In France, Italy, the United States, and Australia, RSV outbreaks alternated with COVID-19 epidemic waves; strict restrictions during COVID-19 surges flattened RSV activity, whereas relaxed measures between waves allowed RSV resurgence [
1,
2].
“Upsurge” pattern: Perhaps most concerning was the observation of some infections reaching unprecedented peaks exceeding pre-pandemic levels. In Japan, RSV bronchiolitis cases rose dramatically from just 570 in 2020 to over 10,000 by mid-2021. New Zealand reported RSV incidence rates threefold higher than 2015–2019 levels following the relaxation of border restrictions in April 2021, resulting in increased hospitalizations and intensive care unit (ICU) admissions. Similarly, Australia witnessed RSV peaks surpassing median seasonal levels recorded from 2012–2019 [
2].
The timing and demographic impacts of these resurgences revealed distinctive trends. In Australia, the median age of RSV-infected patients in 2020 increased to 18.4 months, significantly higher than the historical range of 7.3–12.5 months observed between 2012–2019. This shift likely reflects the increased pool of older RSV-naive children who missed typical exposure during restriction periods. Similarly, RSV-related hospitalizations disproportionately increased among children aged 24–59 months compared to younger children, indicating delayed first infections. Resurgence patterns extended beyond RSV to other respiratory and non-respiratory pathogens. After 2 years of historically low circulation, influenza infections notably rebounded in 2022, frequently coinciding with declining SARS-CoV-2 infections. Pediatric IPD incidence also surged, with England reporting IPD incidence in 2021 (1.96/100,000) exceeding pre-pandemic levels (1.43/100,000 in 2017–2019). Germany similarly reported IPD rates surpassing average monthly values from 2015–2019 by 9% during April–June 2021 [
2].
Enterovirus infections exhibited similar trajectories. France reported 3,403 hand, foot, and mouth disease (HFMD) cases from January to September 2021, marking a 47% increase compared to the same period in 2018–2019. Eighteen European countries documented rising enterovirus positivity rates, increasing from 2.5% in January to 8.2% in September 2021, with enterovirus-D68 positivity notably rising from 0.2% to 14%. Brazil experienced a significant HFMD outbreak linked to the resurgence of Coxsackievirus A6 after relaxing non-pharmaceutical interventions [
2].
Another troubling development has been the increased prevalence of viral co-infections. In one Italian study, approximately 30% of respiratory infection cases involved dual viral infections, with 7% involving triple infections—rates substantially higher than those observed pre-pandemic [
1,
2]. This increased co-infection rate likely reflects the simultaneous circulation of multiple previously suppressed viruses (
Table 2).
4. The immunity debt hypothesis: understanding the rebound
The concept of “immunity debt” has emerged as a compelling framework to explain these resurgence patterns. This hypothesis posits that reduced exposure to common pathogens during pandemic restrictions led to diminished population immunity, resulting in a larger susceptible pool and potentially more severe disease upon re-exposure (
Figure 1).
Previously documented following the 2009 H1N1 influenza pandemic, this phenomenon affected RSV seasonality, initially delaying RSV epidemic onset, followed by subsequent surges in subsequent years [
1,
2]. The unprecedented scale and duration of COVID-19 restrictions magnified this effect across multiple pathogens simultaneously.
Children, especially those born during or shortly before the pandemic, experienced critical developmental periods without typical exposure to common pathogens essential for immune system maturation. Consequently, cohorts of immunologically naive children became susceptible to infections typically encountered earlier in life. The observed age shift in RSV and other infections supports this hypothesis—the median age of children hospitalized with RSV increased significantly, indicating delayed first infections [
2].
Immunity debt appears to have influenced not only infection incidence but also disease severity. In New Zealand, RSV-associated hospitalization and ICU admission rates were significantly elevated post-restrictions compared to historical averages [
2]. This pattern suggests that delayed pathogen exposure might be linked to more severe clinical outcomes in some cases.
5. Current challenges and future implications
The altered landscape of pediatric infectious diseases presents several significant challenges for healthcare systems and providers. First, the asynchronous resurgence of multiple pathogens has strained healthcare resources, particularly in pediatric emergency departments and inpatient units. An analysis of pediatric emergency department census data indicated a substantial rebound in 2021 and 2022, with census peaks occurring significantly earlier than pre-pandemic trends. After the reopening of schools without mask mandates, the positivity rate for respiratory pathogens rose to 4.71%, surpassing pre-pandemic levels [
5].
Second, disruptions in typical seasonal patterns have complicated clinical decision-making and resource allocation. Healthcare systems traditionally prepare for predictable seasonal increases in specific illnesses, but the unpredictable timing of recent resurgences has challenged these standard approaches. The simultaneous circulation of SARS-CoV-2 alongside other resurgent pathogens has further complicated diagnostic and treatment scenarios.
Third, these patterns have exposed potential vulnerabilities in current infectious disease surveillance systems. Traditional surveillance methods based on historical seasonal patterns may be insufficient in this new epidemiological landscape. Enhanced, real-time monitoring systems are likely required to rapidly detect and respond to changing infectious disease dynamics.
The experiences of the past 3 years have also raised critical questions about finding the optimal balance of infection control measures in pediatric populations. Although COVID-19 restrictions clearly reduced short-term morbidity from various infectious diseases, subsequent resurgence patterns highlight possible longer-term consequences of disrupted normal pathogen exposure. This introduces complex risk-benefit considerations for public health authorities contemplating infection control strategies during future epidemics.
For vulnerable pediatric populations, including children with immunocompromising conditions and transplant recipients, these shifting epidemiological patterns present unique challenges. Pediatric transplant infectious disease specialists have had to rapidly adapt to these changes [
6]. The concurrent circulation of multiple respiratory viruses significantly increases risks for these groups, underscoring the need for tailored preventive strategies.
6. Preventive strategies moving forward
Navigating this changed landscape of pediatric infectious diseases requires careful consideration of several preventive strategies. Maintaining high vaccination coverage rates for both COVID-19 and routine childhood immunizations remains essential. The disruption of routine immunization services during the pandemic has heightened vulnerability to vaccine-preventable diseases, compounding concerns about immunity debt [
7].
Sustained emphasis on basic infection prevention measures, particularly hand hygiene, remains crucial. Although stringent social distancing measures have largely been relaxed, selective implementation of protective measures during periods of heightened transmission could help mitigate future disease surges. In healthcare settings, diagnostic stewardship and antimicrobial stewardship have become increasingly important as infection patterns evolve [
8].
Enhanced surveillance systems capable of promptly detecting shifts in disease patterns can facilitate timely and targeted interventions. Wastewater monitoring and other population-level surveillance approaches may complement traditional clinical surveillance methods [
1]. For respiratory infections specifically, developing combination vaccines and therapeutics addressing multiple pathogens simultaneously could significantly assist in managing the complexities of the post-pandemic landscape.
7. Conclusion
The COVID-19 pandemic has profoundly altered pediatric infectious disease epidemiology, creating a dynamic and at times unpredictable landscape. The direct impact of SARS-CoV-2 on children has evolved in tandem with emerging variants and vaccination uptake, while indirect effects on other infectious diseases have emerged through dramatic suppression followed by intricate resurgence patterns.
The immunity debt hypothesis offers a valuable framework for interpreting these shifts; however, many questions about the long-term implications for pediatric health remain unanswered. Navigating this evolving landscape will require flexible and responsive healthcare systems, robust surveillance infrastructures, and thoughtful implementation of preventive measures.
Clinicians caring for children must remain aware of these changed epidemiological patterns to guide diagnostic evaluations, clinical management, and anticipatory counseling effectively. The lessons learned during this pandemic period will undoubtedly influence future infection prevention and control strategies, highlighting both the intended and unintended consequences of widespread public health interventions on pediatric infectious disease epidemiology.
ARTICLE INFORMATION
Figure 1.Proposed mechanism of “immunity debt” and post-pandemic infectious disease resurgence. The figure illustrates how pandemic restrictions reduced pathogen circulation, leading to decreased population immunity, followed by increased susceptibility and more severe disease upon re-exposure after restrictions were lifted. COVID-19, coronavirus disease 2019.
Table 1.Comparison of the impact of COVID-19 on children across variant periods
|
Characteristic |
Pre-Alpha/Alpha period (2020) |
Delta period (2021) |
Omicron period (2022–2023) |
|
Infection rate |
Lower; children less affected than adults |
Increased pediatric cases; more transmissible in children |
Highest pediatric rates; significant transmission in school settings |
|
Symptom severity |
51%–62% required hospital admission; 7%–8% ICU admission |
Most children (58%) had mild symptoms; 36% were asymptomatic |
Further reduction in severity; hospitalization risk approximately 1/3 of Delta period |
|
Age distribution |
Relatively even across pediatric age groups |
Increasing cases in school-age children |
Significant increase in infants <1 year (42.2% of admissions in the United Kingdom) |
|
Vaccination impact |
No pediatric vaccine available |
Vaccination began for adolescents; hospitalization rates 0.02%–0.2% in vaccinated |
Extended to children >6 months; continued protection against severe disease |
|
Long-term sequelae |
MIS-C emerged as a significant complication |
MIS-C continued but better recognized and treated |
Reduced MIS-C incidence; emerging concerns about post-COVID-19 conditions |
Table 2.Changes in pediatric infectious disease patterns across COVID-19 pandemic phases
|
Disease |
Pre-COVID-19 (2018–2019) |
During restrictions (2020) |
Post-restrictions (2021–2023) |
|
RSV bronchiolitis |
Predictable winter seasonality; primarily affected infants <12 months |
Dramatic decline (>90% reduction in many regions); minimal seasonal pattern |
Off-season emergence; higher median patient age; infection rates exceeding pre-pandemic levels by up to 300% |
|
Influenza |
Annual winter epidemics; significant pediatric morbidity |
Near disappearance in most regions; >99% reduction in some countries |
Delayed resurgence; alternating patterns with COVID-19; severe season in 2022–2023 |
|
Invasive pneumococcal disease |
Stable endemic rates with seasonal variations |
50%–65% reduction from baseline |
Exceeded pre-pandemic levels in some regions; 1.96/100,000 vs. 1.43/100,000 in England |
|
Enterovirus infections (including HFMD) |
Summer-fall seasonality; stable annual rates |
Very low prevalence |
Large-scale outbreaks; 47% increase in France compared to 2018–2019 |
|
Multiple respiratory virus co-infections |
Uncommon (<10% of positive cases) |
Rare |
Increased frequency; 30% dual infections and 7% triple infections in some cohorts |
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